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1.
Diabetes Technol Ther ; 26(5): 335-340, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38315502

RESUMO

Older adults with type 1 diabetes may face challenges driving safely. Glucose "above-5-to-drive" is often recommended for insulin-treated diabetes to minimize hypoglycemia while driving. However, the effectiveness of this recommendation among older adults has not been evaluated. Older drivers with type 1 diabetes were assessed while using sensor-augmented insulin pumps during a 2-week clinical trial run-in. Twenty-three drivers (median age 69 years [interquartile range; IQR 65-72]; diabetes duration 37 years [20-45]) undertook 618 trips (duration 10 min [5-21]). Most trips (n = 535; 87%) were <30 min duration; 9 trips (1.5%) exceeded 90 min and 3 trips (0.5%) exceeded 120 min. Pre-trip continuous glucose monitoring (CGM) was >5.0 mmol/L for 577 trips (93%) and none of these had CGM <3.9 mmol/L during driving (including 8 trips >90 min and 3 trips >120 min). During 41 trips with pre-trip CGM ≤5.0 mmol/L, 11 trips had CGM <3.9 mmol/L. Seventy-one CGM alerts occurred during 60 trips (10%), of which 54 of 71 alerts (76%) were unrelated to hypoglycemia. Our findings support a glucose "above-5-to-drive" recommendation to avoid CGM-detected hypoglycemia among older drivers, including for prolonged drives, and highlight the importance of active CGM low-glucose alerts to prevent hypoglycemia during driving. Driving-related CGM usability and alert functionality warrant investigation. Clinical trial ACTRN1261900515190.


Assuntos
Condução de Veículo , Automonitorização da Glicemia , Glicemia , Diabetes Mellitus Tipo 1 , Hipoglicemia , Hipoglicemiantes , Sistemas de Infusão de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Idoso , Masculino , Feminino , Glicemia/análise , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Insulina/uso terapêutico , Pessoa de Meia-Idade
2.
Sci Rep ; 12(1): 8997, 2022 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-35637212

RESUMO

Numerous organisms use the Earth's magnetic field as a sensory cue for migration, body alignment, or food search. Despite some contradictory reports, yet it is generally accepted that humans do not sense the geomagnetic field. Here, we demonstrate that a magnetic field resonance mechanism mediates light-dependent magnetic orientation in men, using a rotary chair experiment combined with a two-alternative forced choice paradigm. Two groups of subjects were classified with different magnetic orientation tendencies depending on the food context. Magnetic orientation of the subjects was sensitive to the wavelength of incident light and was critically dependent on blue light reaching the eyes. Importantly, it appears that a magnetic field resonance-dependent mechanism mediates these responses, as evidenced by disruption or augmentation of the ability to orient by radiofrequency magnetic fields at the Larmor frequency and the dependence of these effects on the angle between the radiofrequency and geomagnetic fields. Furthermore, inversion of the vertical component of the geomagnetic field revealed a non-canonical inclination compass effect on the magnetic orientation. These results establish the existence of a human magnetic sense and suggest an underlying quantum mechanical magnetoreception mechanism.


Assuntos
Campos Magnéticos , Orientação , Humanos , Magnetismo , Masculino , Orientação/fisiologia , Ondas de Rádio , Vibração
3.
Biol Psychiatry ; 91(7): 676-689, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34961622

RESUMO

BACKGROUND: The reward system regulates motivated behavior, and repeated practice of specific motivated behavior might conversely modify the reward system. However, the detailed mechanisms by which they reciprocally regulate each other are not clearly understood. METHODS: Mice subjected to chronic restraint stress show long-lasting depressive-like behavior, which is rescued by continual engagement with playable objects. A series of molecular, pharmacological, genetic, and behavioral analyses, combined with microarray, liquid chromatography, and chemogenetic tools, are used to investigate the neural mechanisms of antidepressive effects of playable objects. RESULTS: Here, we show that repeated restraint induces dopamine surges into the nucleus accumbens-lateral shell (NAc-lSh), which cause upregulation of the neuropeptide PACAP in the NAc-lSh. As repeated stress is continued, the dopamine surge by stressors is adaptively suppressed without restoring PACAP upregulation, and the resulting enhanced PACAP inputs from NAc-lSh neurons to the ventral pallidum facilitate depressive-like behaviors. Continual engagement with playable objects in mice subjected to chronic stress remediates reduced dopamine response to new stressors, enhanced PACAP upregulation, and depressive-like behaviors. Overactivation of dopamine D1 receptors over the action of D2 receptors in the NAc-lSh promotes depressive-like behaviors. Conversely, inhibition of D1 receptors or PACAP upregulation in the NAc-lSh confers resilience to chronic stress-induced depressive-like behaviors. Histochemical and chemogenetic analyses reveal that engagement with playable objects produces antidepressive effects by reshaping the ventral tegmental area-to-NAc-lSh and NAc-lSh-to-ventral pallidum circuits. CONCLUSIONS: These results suggest that behavioral engagement with playable objects remediates depressive-like behaviors by resolving stress-induced maladaptive changes in the reward system.


Assuntos
Dopamina , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Animais , Antidepressivos/farmacologia , Camundongos , Núcleo Accumbens , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Recompensa , Área Tegmentar Ventral
4.
Nat Commun ; 12(1): 6682, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795225

RESUMO

Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues defective glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior.


Assuntos
Agressão/fisiologia , Transtorno Depressivo/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Estresse Psicológico/fisiopatologia , Agressão/psicologia , Animais , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Corticosterona/sangue , Corticosterona/metabolismo , Corticosterona/farmacologia , Transtorno Depressivo/psicologia , Feminino , Perfilação da Expressão Gênica/métodos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores de Mineralocorticoides/genética , Receptores de Mineralocorticoides/metabolismo , Restrição Física , Fatores de Tempo
5.
Exp Neurobiol ; 30(6): 415-429, 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-34983882

RESUMO

Hyperoxygenation therapy remediates neuronal injury and improves cognitive function in various animal models. In the present study, the optimal conditions for hyperoxygenation treatment of stress-induced maladaptive changes were investigated. Mice exposed to chronic restraint stress (CRST) produce persistent adaptive changes in genomic responses and exhibit depressive-like behaviors. Hyperoxygenation treatment with 100% O2 (HO2) at 2.0 atmospheres absolute (ATA) for 1 h daily for 14 days in CRST mice produces an antidepressive effect similar to that of the antidepressant imipramine. In contrast, HO2 treatment at 2.0 ATA for 1 h daily for shorter duration (3, 5, or 7 days), HO2 treatment at 1.5 ATA for 1 h daily for 14 days, or hyperbaric air treatment at 2.0 ATA (42% O2) for 1 h daily for 14 days is ineffective or less effective, indicating that repeated sufficient hyperoxygenation conditions are required to reverse stress-induced maladaptive changes. HO2 treatment at 2.0 ATA for 14 days restores stress-induced reductions in levels of mitochondrial copy number, stress-induced attenuation of synaptophysin-stained density of axon terminals and MAP-2-staining dendritic processes of pyramidal neurons in the hippocampus, and stress-induced reduced hippocampal neurogenesis. These results suggest that HO2 treatment at 2.0 ATA for 14 days is effective to ameliorate stress-induced neuronal and behavioral deficits.

6.
Commun Biol ; 3(1): 292, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32504071

RESUMO

Brain aging proceeds with cellular and molecular changes in the limbic system. Aging-dependent changes might affect emotion and stress coping, yet the underlying mechanisms remain unclear. Here, we show aged (18-month-old) mice exhibit upregulation of NADPH oxidase and oxidative stress in the hippocampus, which mirrors the changes in young (2-month-old) mice subjected to chronic stress. Aged mice that lack p47phox, a key subunit of NADPH oxidase, do not show increased oxidative stress. Aged mice exhibit depression-like behavior following weak stress that does not produce depressive behavior in young mice. Aged mice have reduced expression of the epigenetic factor SUV39H1 and its upstream regulator p-AMPK, and increased expression of Ppp2ca in the hippocampus-changes that occur in young mice exposed to chronic stress. SUV39H1 mediates stress- and aging-induced sustained upregulation of p47phox and oxidative stress. These results suggest that aging increases susceptibility to stress by upregulating NADPH oxidase in the hippocampus.


Assuntos
Envelhecimento , Depressão/patologia , NADPH Oxidases/fisiologia , Estresse Oxidativo , Estresse Fisiológico , Animais , Comportamento Animal , Depressão/etiologia , Depressão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxirredução , Espécies Reativas de Oxigênio/metabolismo
7.
Int J Mol Sci ; 21(3)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028744

RESUMO

The human specific bacterial pathogen Helicobacter pylori (H. pylori) is associated with severe gastric diseases, including gastric cancer. Recently, the increasing resistance makes the usage of antibiotics less effectively. Therefore, development of a new antimicrobial agent is required to control H. pylori infection. In the current study, the inhibitory effect of ß-caryophyllene on H. pylori growth, as well as the antibacterial therapeutic effect, has been demonstrated. ß-caryophyllene inhibited H. pylori growth via the downregulation of dnaE, dnaN, holB, and gyrA and also downregulated virulence factors such as CagA, VacA, and SecA proteins. ß-caryophyllene inhibited expression of several T4SS components, so that CagA translocation into H. pylori-infected AGS gastric cancer cells was decreased by ß-caryophyllene treatment. ß-caryophyllene also inhibited VacA entry through the downregulation of T5aSS. After ß-caryophyllene administration on Mongolian gerbils, the immunohistochemistry (IHC) and Hematoxylin&Eosin stains showed therapeutic effects in the treated groups. Hematological data, which was consistent with histological data, support the therapeutic effect of ß-caryophyllene administration. Such a positive effect of ß-caryophyllene on H. pylori infection potently substantiates the natural compound as being capable of being used as a new antimicrobial agent or functional health food to help patients who are suffering from gastroduodenal diseases due to H. pylori infection.


Assuntos
Adenocarcinoma/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Sesquiterpenos Policíclicos/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Feminino , Gerbillinae , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Humanos , Técnicas In Vitro , Masculino , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
8.
Proc Natl Acad Sci U S A ; 117(2): 1216-1222, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31889001

RESUMO

Certain long-distance migratory animals, such as salmon and sea turtles, are thought to imprint on the magnetic field of their natal area and to use this information to help them return as adults. Despite a growing body of indirect support for such imprinting, direct experimental evidence thereof remains elusive. Here, using the fruit fly as a magnetoreceptive model organism, we demonstrate that exposure to a specific geographic magnetic field during a critical period of early development affected responses to a matching magnetic field gradient later in life. Specifically, hungry flies that had imprinted on a specific magnetic field from 1 of 3 widely separated geographic locations responded to the imprinted field, but not other magnetic fields, by moving downward, a geotactic behavior associated with foraging. This same behavior occurred spontaneously in the progeny of the next generation: female progeny moved downward in response to the field on which their parents had imprinted, whereas male progeny did so only in the presence of these females. These results represent experimental evidence that organisms can learn and remember a magnetic field to which they were exposed during a critical period of development. Although the function of the behavior is not known, one possibility is that imprinting on the magnetic field of a natal area assists flies and their offspring in recognizing locations likely to be favorable for foraging and reproduction.


Assuntos
Migração Animal/fisiologia , Drosophila/fisiologia , Campos Magnéticos , Animais , Feminino , Comportamento de Retorno ao Território Vital/fisiologia , Fixação Psicológica Instintiva/fisiologia , Masculino , Reprodução
9.
Int J Mol Sci ; 21(24)2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33419292

RESUMO

In this study, hydrogen generation powder samples were prepared using zinc carbonate as a precursor, at a temperature varying from 400 to 700 °C in H2 atmosphere, and were characterized in terms of antioxidant activity. The concentration of dissolved hydrogen obtained by the powder samples was measured using a dissolved hydrogen meter as a function of time. In addition, the antioxidant activity of the samples was evaluated based on the Oyaizu's method, removal rate of ·OH radicals, and ferric reducing antioxidant power. Finally, the hydrogen mask pack was fabricated using the hydrogen generation powder sample and gel-type emulsion. In the clinical test on the mask pack, the effect of the mask on skin aging was characterized and compared to that of a commercial sample. The skin densities of the participants in the experimental group and the control group increased by 18.41% and 9.93% after 4 weeks, respectively. The improved skin density of the participants who used the hydrogen mask pack in the experimental group, might be attributed to the recovery effect of the hydrogen molecule in the mask pack on the denatured thick skin layer.


Assuntos
Antioxidantes/química , Carbonatos/química , Hidrogênio/química , Pele/efeitos dos fármacos , Compostos de Zinco/química , Antioxidantes/farmacologia , Emulsões/química , Emulsões/farmacologia , Humanos , Radical Hidroxila/química , Ferro/química , Pós/química , Pós/farmacologia , Pele/patologia , Envelhecimento da Pele/efeitos dos fármacos , Temperatura , Água/química
10.
Mol Neurobiol ; 56(12): 8537-8556, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31267372

RESUMO

Chronic stress induces persistent depressive behaviors. Stress-induced transcriptional alteration over the homeostatic range in stress hormone-sensitive brain regions is believed to underlie long-lasting depressive behaviors. However, the detailed mechanisms by which chronic stress causes those adaptive changes are not clearly understood. In the present study, we investigated whether epigenetic changes regulate stress-induced depressive behaviors. We found that chronic stress in mice downregulates the epigenetic factors HDAC2 and SUV39H1 in the hippocampus. A series of follow-up analyses including ChIP assay and siRNA-mediated functional analyses reveal that glucocorticoids released by stress cumulatively increase Mkp-1 expression in the hippocampus, and increased Mkp-1 then debilitates p-CREB and PPARγ, which in turn suppress the epigenetic factors HDAC2 and SUV39H1. Furthermore, HDAC2 and SUV39H1 normally suppress the transcription of the Mkp-1, and therefore the reduced expression of HDAC2 and SUV39H1 increases Mkp-1 expression. Accordingly, repeated stress progressively strengthens a vicious cycle of the Mkp-1 signaling cascade that facilitates depressive behaviors. These results suggest that the hippocampal stress adaptation system comprising HDAC2/SUV39H1-regulated Mkp-1 signaling network determines the vulnerability to chronic stress and the maintenance of depressive behaviors.


Assuntos
Comportamento Animal , Depressão/etiologia , Depressão/genética , Fosfatase 1 de Especificidade Dupla/metabolismo , Epigênese Genética , Hipocampo/metabolismo , Estresse Psicológico/complicações , Animais , Linhagem Celular , Doença Crônica , Cinamatos/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Depsídeos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Epigênese Genética/efeitos dos fármacos , Histona Desacetilase 2/metabolismo , Masculino , Metiltransferases/metabolismo , Camundongos Endogâmicos C57BL , PPAR gama/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Repressoras/metabolismo , Restrição Física , Regulação para Cima/efeitos dos fármacos , Ácido Rosmarínico
11.
ACS Comb Sci ; 21(6): 482-488, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31009197

RESUMO

Preparation of 2,4,5-trisubstituted thiazole derivatives via a new solid-phase synthetic route has been conducted in this study. The synthetic route begins with the synthesis of a core skeleton 2,4-diamino(thiazol-5-yl)-substituted phenylmethanone resin obtained through a cyclization reaction with a carbamimidothioate linker. The core skeleton was substituted with diverse building blocks such as amines, alkyl halides, and acid chlorides. The products were cleaved from the solid support via a TFA/CH2Cl2 cleavage cocktail. Overall, the strategy permits the incorporation of three points of diversity into the thiazole ring system with good overall yields ( Lee , T. ; et al. J. Comb. Chem. 2009 , 11 ( 2 ), 288 - 293 ). Finally, the library of 2,4,5-trisubstituted thiazole derivatives showed oral bioavailability through calculation of the physicochemical properties.


Assuntos
Tiazóis/síntese química , Aminas/química , Técnicas de Química Combinatória , Estrutura Molecular , Bibliotecas de Moléculas Pequenas/síntese química , Técnicas de Síntese em Fase Sólida
12.
ACS Comb Sci ; 21(5): 380-388, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-30848875

RESUMO

In this study, we synthesized 2-amino-5-carboxamide thiazole derivatives on solid phase. The synthesis of the library starts with the reductive amination of the 4-formyl-3-methoxy phenoxy resin to prevent isomer formation. The dehydrative cyclization of thiourea intermediate resin, which is the key step in the synthetic process, was successfully synthesized using α-bromoketone in the presence of the DMF so as to afford 2-amino-5-carboxylate thiazole resin. The resulting resin is coupled with various amines. Finally, the 2-amino-5-carboxamide thiazole resin was cleaved from the polymer support using a TFA and DCM cocktail. The physicochemical properties of the proposed 2-amino-5-carboxamide thiazole derivatives were calculated and showed potential to be an reasonable oral bioavailability drug properties as determined by Lipinski's Rule.


Assuntos
Técnicas de Síntese em Fase Sólida/métodos , Tiazóis/síntese química , Tioureia/química , Aminas/química , Técnicas de Química Combinatória , Ciclização , Oxirredução , Resinas Sintéticas/química , Tiazóis/química
13.
Int J Mol Sci ; 20(5)2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30866458

RESUMO

H. pylori is classified as a group I carcinogen by WHO because of its involvement in gastric cancer development. Several reports have suggested anti-bacterial effects of menadione, although the effect of menadione on major virulence factors of H. pylori and H. pylori-induced inflammation is yet to be elucidated. In this study, therefore, we demonstrated that menadione has anti-H. pylori and anti-inflammatory effects. Menadione inhibited growth of H. pylori reference strains and clinical isolates. Menadione reduced expression of vacA in H. pylori, and translocation of VacA protein into AGS (gastric adenocarcinoma cell) was also decreased by menadione treatment. This result was concordant with decreased apoptosis in AGS cells infected with H. pylori. Moreover, cytotoxin-associated protein A (CagA) translocation into H. pylori-infected AGS cells was also decreased by menadione. Menadione inhibited expression of several type IV secretion system (T4SS) components, including virB2, virB7, virB8, and virB10, that are responsible for translocation of CagA into host cells. In particular, menadione inhibited nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation and thereby reduced expression of the proinflammatory cytokines such as IL-1ß, IL-6, IL-8, and TNF-α in AGS as well as in THP-1 (monocytic leukemia cell) cell lines. Collectively, these results suggest the anti-bacterial and anti-inflammatory effects of menadione against H. pylori.


Assuntos
Infecções por Helicobacter/imunologia , Helicobacter pylori/efeitos dos fármacos , NF-kappa B/metabolismo , Vitamina K 3/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Calgranulina A/genética , Calgranulina A/metabolismo , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/crescimento & desenvolvimento , Humanos , Testes de Sensibilidade Microbiana , Transporte Proteico/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
14.
Clin Exp Ophthalmol ; 47(5): 588-597, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30788894

RESUMO

IMPORTANCE: Bleb-associated endophthalmitis is a potentially vision-threatening complication of trabeculectomy. With improvements in surgical technique and changing patterns of intraoperative antimetabolite use, a re-evaluation of the incidence of bleb-associated endophthalmitis is warranted. BACKGROUND: To investigate changes in the incidence, presentation, management and outcomes of bleb-associated endophthalmitis between 1997 and 2015 in Victoria, Australia. DESIGN: A retrospective cohort analysis. PARTICIPANTS: Consecutive cases of bleb-associated endophthalmitis managed at the Royal Victorian Eye and Ear Hospital (RVEEH) between 1997 and 2015. METHODS: Medical record review of consecutive cases of bleb-associated endophthalmitis and statistical analysis were performed. MAIN OUTCOME MEASURES: Visual acuity, including loss of light perception, intraocular pressure, and need for further surgery. RESULTS: Sixty-seven eyes with bleb-associated endophthalmitis (BAE) were identified. Of these, 41 had trabeculectomy performed in Victoria during the study period, over which time 11 129 trabeculectomies were performed. The proportion of BAE was stable over time (0.4%). The mean age at presentation was 73.7 ± 12.1 years old and the majority of patients were Caucasian (79.1%). The mean duration between glaucoma filtration surgery and the development of bleb-associated endophthalmitis was 3 years (Interquartile Range = 0.4-6.0 years). The cultures were positive in 71.6% of cases. Approximately 1 in 8 patients required enucleation. The final visual acuity was poor with a Snellen Visual Acuity (VA) of 6/60 or worse in two-thirds of patients. CONCLUSIONS AND RELEVANCE: Bleb-associated endophthalmitis is an uncommon complication following glaucoma filtration surgery. The proportion has remained stable over time. Visual outcomes remain poor.


Assuntos
Endoftalmite , Infecções Oculares Bacterianas , Complicações Pós-Operatórias , Trabeculectomia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Endoftalmite/diagnóstico , Endoftalmite/epidemiologia , Endoftalmite/terapia , Síndrome de Exfoliação/cirurgia , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/terapia , Feminino , Glaucoma de Ângulo Fechado/cirurgia , Glaucoma de Ângulo Aberto/cirurgia , Glucocorticoides/uso terapêutico , Humanos , Incidência , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Vitória/epidemiologia , Transtornos da Visão/diagnóstico , Transtornos da Visão/etiologia , Acuidade Visual/fisiologia
15.
Aging Cell ; 18(2): e12888, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30746828

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aß-induced pathology and progressive cognitive decline. The incidence of AD is growing globally, yet a prompt and effective remedy is not available. Aging is the greatest risk factor for AD. Brain aging proceeds with reduced vascularization, which can cause low oxygen (O2 ) availability. Accordingly, the question may be raised whether O2 availability in the brain affects AD pathology. We found that Tg-APP/PS1 mice treated with 100% O2 at increased atmospheric pressure in a chamber exhibited markedly reduced Aß accumulation and hippocampal neuritic atrophy, increased hippocampal neurogenesis, and profoundly improved the cognitive deficits on the multiple behavioral test paradigms. Hyperoxygenation treatment increased the expression of BDNF, NT3, and NT4/5 through the upregulation of MeCP2/p-CREB activity in HT22 cells in vitro and in the hippocampus of mice. In contrast, siRNA-mediated inhibition of MeCP2 or TrkB neurotrophin receptors in the hippocampal subregion, which suppresses neurotrophin expression and neurotrophin action, respectively, blocked the therapeutic effects of hyperoxygenation on the cognitive impairments of Tg-APP/PS1 mice. Our results highlight the importance of the O2 -related mechanisms in AD pathology, which can be revitalized by hyperoxygenation treatment, and the therapeutic potential of hyperoxygenation for AD.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Peróxidos/farmacologia , Regulação para Cima/efeitos dos fármacos , Fatores Etários , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , Camundongos Transgênicos , Oxigênio/metabolismo
16.
Biosci Biotechnol Biochem ; 83(1): 166-173, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30286691

RESUMO

Inflammation induced by Helicobacter pylori infection related to gastric carcinogenesis. In this study, we have investigated the anti-inflammatory effect and its mechanism of kaempferol in the inflammatory response caused by H. pylori infection in vitro. We found that kaempferol reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-8) and production of IL-8 in AGS cells. In addition, kaempferol suppressed translocation of cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) of H. pylori to AGS cells. It was due to decreased transcription of type IV secretion system (T4SS) components involved in CagA injection and secretion system subunit protein A (SecA) of type V secretion system (T5SS) involved in VacA secretion by kaempferol. In conclusion, kaempferol shows the anti-inflammatory effect by suppressing the translocation of CagA and VacA proteins and leading to the down-regulation of pro-inflammatory cytokines. Abbreviations: CagA: cytotoxin-associated gene A; VacA: vacuolating cytotoxin A; T4SS: type IV secretion systems; SecA: secretion system subunit protein A; T5SS: type V secretion system.


Assuntos
Anti-Inflamatórios/farmacologia , Gastrite/microbiologia , Gastrite/prevenção & controle , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Inflamação/prevenção & controle , Quempferóis/farmacologia , Antígenos de Bactérias/efeitos dos fármacos , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/crescimento & desenvolvimento , Humanos , Inflamação/etiologia , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/biossíntese , Interleucina-8/metabolismo , Transporte Proteico/efeitos dos fármacos , Fator de Crescimento Transformador alfa/metabolismo
17.
RSC Adv ; 9(18): 10297-10304, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35520897

RESUMO

While Li2MnO3 as an over-lithiated layered oxide (OLO) shows a significantly high reversible capacity of 250 mA h g-1 in lithium-ion batteries (LIBs), it has critical issues of poor cycling performance and deteriorated high rate performance. In this study, modified OLO cathode materials for improved LIB performance were obtained by heating the as-prepared OLO at different temperatures (400, 500, and 600 °C) in the presence of polyvinylpyrrolidone (PVP) under an N2 atmosphere. Compared to the as-prepared OLO, the OLO sample heated at 500 °C with PVP exhibited a high initial discharge capacity of 206 mA h g-1 and high rate capability of 111 mA h g-1 at 100 mA g-1. The superior performance of the OLO sample heated at 500 °C with PVP is attributed to an improved electronic conductivity and Li+ ionic motion, resulting from the formation of the graphitic carbon structure and increased Mn3+ ratio during the decomposition of PVP.

18.
J Wound Ostomy Continence Nurs ; 44(6): 572-577, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29117084

RESUMO

PURPOSE: The purpose of this study was to explore the self-management experiences of Korean women with urinary incontinence (UI). DESIGN: Descriptive, qualitative study using focus groups. SUBJECTS AND SETTING: Twenty-two community-dwelling women, 65 years and older, participated in 3 focus-group interviews. Participants were recruited from 2 elderly halls and 1 senior welfare center in South Korea. METHODS: Three focus group interviews comprising 6 to 8 individuals were conducted in a quiet venue at the elderly hall or senior welfare center. Two investigators performed the interviews; one acted as moderator and one as notetaker; interviews began with scripted open-ended questions. All interviews were electronically recorded and transcribed verbatim. Using an inductive thematic approach, data were first analyzed by the first and second authors; and all 4 authors contributed to coding and agreed on final themes. RESULTS: Korean women perceived UI as a loss of dignity, an odor problem, an uncontrollable disease, and a life impairment. Thematic analysis revealed 4 themes regarding the self-management experience of UI: preserving self-respect in the sociocultural environment, deodorizing the smell, keeping the secret of uncontrollability, and adjusting to an impaired life. CONCLUSIONS: Women in this study used various daily-living strategies to manage UI, but they mainly implemented strategies to keep UI a secret, including restrictions in activities of daily living. Educational approaches are needed to inform women with UI about more effective management skills.


Assuntos
Qualidade de Vida/psicologia , Autogestão/psicologia , Incontinência Urinária/psicologia , Incontinência Urinária/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Grupos Focais , Humanos , Odorantes , Pessoalidade , Pesquisa Qualitativa , República da Coreia
19.
ChemSusChem ; 10(10): 2202-2209, 2017 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28296248

RESUMO

To develop doped carbon nanostructures as non-precious metal cathode catalysts, nanocomposites were synthesized by using SBA-15 and 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin-iron(III) chloride with different ratios of amorphous MoS2 precursor. From various analyses, it was found that, during pyrolysis at 900 °C under an N2 atmosphere, the amorphous MoS2 precursor decomposed into Mo and S, facilitating the formation of graphene sheet-like carbon with MoC and doping of sulfur in the carbon. In the nanocomposite formed from 10 wt % MoS2 precursor (denoted as Mo/S/PC-10), most of the MoS2 was decomposed, thus forming S-doped carbon, which was grown on the MoC phase without crystalline MoS2 . Furthermore, Mo/S/PC-10 exhibited better performance in the oxygen reduction reaction (specific activity of 1.23 mA cm-2 at 0.9 V and half-wave potential of 0.864 V) than a commercial Pt catalyst, owing to a heteroatom-doped carbon nanostructure with a fairly high specific surface area. In the polarization curve of the unit-cell performance measured at 80 °C under ambient pressure, Mo/S/PC-10 as a cathode catalyst exhibited an optimal power density of 314 mW cm-2 and a current density of 280 mA cm-2 at 0.6 V.


Assuntos
Carbono/química , Dissulfetos/química , Molibdênio/química , Nanoestruturas/química , Oxigênio/química , Porfirinas/química , Enxofre/química , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Transmissão , Oxirredução , Difração de Raios X
20.
Clin Exp Ophthalmol ; 45(5): 472-480, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28134460

RESUMO

IMPORTANCE: This study provides ophthalmologists who manage uveitic glaucoma with important information on factors that can affect the success of surgical management of this challenging disease. BACKGROUND: This study examines surgical outcomes of trabeculectomy and glaucoma device implant (GDI) surgery for uveitic glaucoma, in particular the effect of uveitis activity on surgical outcomes. DESIGN: Retrospective chart review at a tertiary institution. SAMPLES: Eighty-two cases with uveitic glaucoma (54 trabeculectomies and 28 (GDI) surgeries) performed between 1 December 2006 and 30 November 2014. METHODS: Associations of factors with surgical outcomes were examined using univariate and multivariate analysis. MAIN OUTCOME MEASURES: Surgical outcomes as defined in Guidelines from World Glaucoma Association. RESULTS: Average follow up was 26.4 ± 21.5 months. Overall qualified success rate of the trabeculectomies was not statistically different from GDI, being 67% and 75%, respectively (P = 0.60). Primary and secondary GDI operations showed similar success rates. The most common postoperative complication was hypotony (~30%). Active uveitis at the time of operation was higher in trabeculectomy compared with GDI group (35% vs. 14%). Active uveitis at the time of surgery did not significantly increase risk of failure for trabeculectomies. Recurrence of uveitis was significantly associated with surgical failure in trabeculectomy group (odds ratio 4.8, P = 0.02) but not in GDI group. CONCLUSIONS AND RELEVANCE: Surgical success rate of GDI was not significantly different from trabeculectomy for uveitic glaucoma in this study. Regular monitoring, early and prolonged intensive treatment of ocular inflammation is important for surgical success particularly following trabeculectomy.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Pressão Intraocular/fisiologia , Trabeculectomia/métodos , Uveíte/complicações , Acuidade Visual , Feminino , Seguimentos , Glaucoma/etiologia , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/cirurgia
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