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1.
BMC Nurs ; 23(1): 228, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38566088

RESUMEN

BACKGROUND: Japan has been accepting foreign nurse candidates since 2008 under Economic Partnership Agreements (EPAs). As globalisation progresses, nurses from diverse backgrounds are expected to play an active role in the medical field. Using an interview survey, this study examined the factors associated with EPA nurses' willingness to continue working in Japan. METHODS: We conducted semi-structured interviews from January 2022 to July 2023 with eight EPA nurses and one EPA nurse candidate working in Japan to investigate the factors associated with foreign-educated nurses' willingness to continue working in Japan. The interview guide included items on the status of the daily performance of their duties, what they found pleasurable in their nursing experience in Japan, difficulties they encountered in carrying out their nursing duties, and their expectations of the Japanese staff around them. Data were analysed using thematic analysis. RESULTS: From the interview data, seven themes were extracted. To continue working in Japan, it was important for EPA nurses to be able to communicate with patients and colleagues, maintain self-esteem and motivation, be resilient, have support from EPA peers and family members, be accepted by others such as patients and colleagues, and be satisfied with the support they received. CONCLUSION: The EPA nurses experienced many difficulties after becoming nurses and tended to be isolated because of their non-Japanese status. The results suggest that not only support from colleagues and supervisors but also a general understanding of EPA nurses from Japanese society is necessary. As globalisation accelerates, the Japanese nursing field needs to understand the diversity of the nursing profession and build a support system that will enable them to continue to take pride and feel motivated in their work.

2.
BMC Pregnancy Childbirth ; 20(1): 760, 2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33287736

RESUMEN

BACKGROUND: Maternal healthcare services in Indonesia have seen dramatic improvements over the past 25 years and yet there is still room for improvement. The perception, by the women, of the perinatal care provided, is a vital input to further improving these services. This study examines how the perinatal care provided is experienced by Japanese women in Bali, using an interview survey. METHODS: We conducted semi-structured interviews, from August to October 2017, with 14 Japanese women living in Badung Regency and Denpasar City in Bali Province, Indonesia to report their perception of the perinatal care they experienced during their pregnancies. The interview guide included among others, the reasons for choosing specific (perinatal care) health facilities and their satisfaction with their experience of using the antenatal, delivery, and postnatal care services. The data were analysed using the qualitative content analysis method. RESULTS: From the interview data, 12 categories across five themes were extracted. Participants reported experiencing various concerns during their pregnancies such as difficulty in obtaining perinatal care related information. From the beginning of their pregnancies, participants gradually established trusting relationships with midwives, but in many situations, they were disappointed with their childbirth experiences, as they felt that the care provided was not woman-centred. Through their own efforts and with the support of family members and other Japanese residents, many women were able to eventually regard their childbirth experiences as positive. Nevertheless, some women could not overcome their negative impressions even years after childbirth. CONCLUSIONS: Participants desired close attention and encouragement from nurses and midwives. Our results suggest that Japanese women in Bali expected a woman-centred perinatal care and active support from nursing/midwifery staff during their pregnancies and postnatal care.


Asunto(s)
Actitud Frente a la Salud , Parto , Prioridad del Paciente , Atención Prenatal/normas , Adulto , Femenino , Humanos , Indonesia/epidemiología , Japón/etnología , Partería/normas , Embarazo , Atención Prenatal/psicología , Relaciones Profesional-Paciente , Investigación Cualitativa
3.
Int J Mol Sci ; 21(15)2020 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-32748844

RESUMEN

Ongoing aortic wall degeneration and subsequent aneurysm exclusion failure are major concerns after an endovascular aneurysm repair with a stent-graft. An ideal solution would be a drug therapy that targets the aortic wall and inhibits wall degeneration. Here, we described a novel drug delivery system, which allowed repetitively charging a graft with therapeutic drugs and releasing them to the aortic wall in vivo. The system was composed of a targeted graft, which was labeled with a small target molecule, and the target-recognizing nanocarrier, which contained suitable drugs. We developed the targeted graft by decorating a biotinylated polyester graft with neutravidin. We created the target-recognizing nanocarrier by conjugating drug-containing liposomes with biotinylated bio-nanocapsules. We successfully demonstrated that the target-recognizing nanocarriers could bind to the targeted graft, both in vitro and in blood vessels of live mice. Moreover, the drug released from our drug delivery system reduced the expression of matrix metalloproteinase-9 in mouse aortas. Thus, this hybrid system represents a first step toward an adjuvant therapy that might improve the long-term outcome of endovascular aneurysm repair.


Asunto(s)
Aorta/efectos de los fármacos , Aneurisma de la Aorta/terapia , Prótesis Vascular , Sistemas de Liberación de Medicamentos/métodos , Metaloproteinasa 9 de la Matriz/metabolismo , Quinolinas/administración & dosificación , Animales , Aorta/metabolismo , Aorta/patología , Avidina/química , Portadores de Fármacos/química , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/química , Masculino , Ratones Endogámicos C57BL , Microscopía Fluorescente , Nanoestructuras/química , Diseño de Prótesis , Quinolinas/química , Resultado del Tratamiento
4.
Alcohol Clin Exp Res ; 43(2): 227-242, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30428137

RESUMEN

BACKGROUND: Alcohol abuse and adherence to atherogenic diet (AD; a low-carbohydrate-high-protein diet) have been positively associated with cardiovascular disease. In addition, it has been demonstrated clinically that dietary intake is increased on days when alcohol is consumed. Here, the additive effects of ethanol (EtOH) and AD on atherosclerosis, a major underlying cause of cardiovascular disease, were investigated in apolipoprotein E/low-density lipoprotein receptor double-knockout (KO) mice. The mechanisms, especially aortic oxidative stress damage, were highlighted. METHODS: Twelve-week-old male KO mice on AD with or without EtOH treatment were bred for 4 months. Age-matched male C57BL/6J mice on a standard chow diet without EtOH treatment served as controls. Analyses were conducted using ultrasound biomicroscopy, histopathological and fluorescence immunohistochemical examinations, Western blots, and polymerase chain reaction. RESULTS: KO mice on AD with EtOH treatment showed increases in aortic maximum intima media thickness, hypoechoic plaque formation, and mean Oil-Red-O content. These results were associated with enhanced ratio of aortic 8-hydroxy-2'-deoxyguanosine (8-OHdG)-immunopositive area to the metallothionein (MT) immunopositive area and suppression of AD-induced up-regulated aortic Mt1, Mt2, and upstream stimulatory factor 1 mRNA expressions. Moreover, 8-OHdG was expressed in the nuclei of CD31- and alpha smooth muscle actin-immunopositive cells, and the up-regulated mRNA expressions of aortic nitric oxide synthase 3 and platelet-derived growth factors were only observed in the KO mice on AD with EtOH treatment. CONCLUSIONS: Alcohol abuse and adherence to AD may promote the shift of aortic oxidative stress and antioxidative stress balance toward oxidative stress predominance and reduced antioxidative stress, which may be partly due to the decrease in MT at the cell biological level and down-regulation of Mt at the gene level, which in turn could play a role in the up-regulation of endothelial dysfunction-related and vascular smooth muscle cell proliferation-related gene expression and the progression of atherosclerosis in mice with hyperlipidemia.


Asunto(s)
Consumo de Bebidas Alcohólicas/patología , Aorta/patología , Apolipoproteínas E/genética , Aterosclerosis/patología , Dieta Aterogénica/efectos adversos , Etanol/efectos adversos , Receptores de LDL/genética , 8-Hidroxi-2'-Desoxicoguanosina/metabolismo , Animales , Aorta/metabolismo , Aterosclerosis/inducido químicamente , Aterosclerosis/metabolismo , Grosor Intima-Media Carotídeo , Masculino , Metalotioneína/biosíntesis , Metalotioneína/metabolismo , Ratones , Ratones Noqueados , Óxido Nítrico Sintasa de Tipo III/biosíntesis , Estrés Oxidativo/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/biosíntesis , Factores Estimuladores hacia 5'/biosíntesis
5.
Graefes Arch Clin Exp Ophthalmol ; 257(9): 1823-1829, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31154470

RESUMEN

PURPOSE: To investigate the anatomical and functional changes in areas containing paravascular abnormalities (PVA) in eyes with epiretinal membrane (ERM) after surgery. METHODS: Twenty-eight eyes with concurrent idiopathic ERM and PVA were enrolled in this prospective study. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and areas of PVA in the superficial and deep capillary levels detected on en face optical coherence tomography were measured preoperatively and 1, 3, and 6 months postoperatively. Retinal sensitivity in selected PVA lesions was evaluated by microperimetry preoperatively and 1 and 6 months postoperatively. RESULTS: The areas of PVA at the superficial capillary level before and 1, 3, and 6 months after surgery measured 1.65 ± 1.27, 0.44 ± 0.62, 0.40 ± 0.64, and 0.38 ± 0.62 mm2, respectively, while those at the deep capillary level measured 0.27 ± 0.57, 0.10 ± 0.26, 0.09 ± 0.29, and 0.05 ± 0.15 mm2, respectively. The areas of PVA in the superficial and deep capillary levels were significantly smaller postoperatively (all p < 0.001 at the superficial capillary level and p = 0.010 at the deep capillary level). Average retinal sensitivity values in the PVA lesions before and 1 and 6 months after surgery were 11.2 ± 3.5, 12.9 ± 3.2, and 13.2 ± 2.7 dB, respectively; the values at postoperative months 1 and 6 were significantly improved (p = 0.045 and p < 0.001, respectively). BCVA and CMT were significantly improved postoperatively. CONCLUSION: PVA not only improves anatomically but also functionally after ERM surgery. Vitrectomy can improve not only central vision but also retinal sensitivity in areas of PVA.


Asunto(s)
Membrana Epirretinal/cirugía , Mácula Lútea/patología , Vasos Retinianos/patología , Agudeza Visual , Vitrectomía/métodos , Anciano , Anciano de 80 o más Años , Capilares/patología , Membrana Epirretinal/diagnóstico , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Prospectivos , Tomografía de Coherencia Óptica
6.
Am J Physiol Heart Circ Physiol ; 315(4): H1012-H1018, 2018 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-30004237

RESUMEN

Abdominal aortic aneurysm (AAA) is a life-threatening disease, and no disease-specific circulating biomarkers for AAA screening are currently available. We have identified a smooth muscle cell (SMC)-specific biomarker for AAA. We cultured aneurysmal tunica media that were collected from eight patients undergoing elective open-repair surgeries. Secreted proteins in culture medium were subjected to liquid chromatography/tandem mass spectrometry. Myosin heavy chain 11 (myosin-11) was identified as a SMC-specific protein in the tunica media-derived secretions of all patients. We then examined myosin-11 protein concentrations by ELISA in plasma samples from patients with AAA ( n = 35) and age-matched healthy control subjects ( n = 34). Circulating myosin-11 levels were significantly higher in patients with AAA than control subjects. The area under the receiver-operating characteristic curve (AUC) of myosin-11 was 0.77, with a specificity of 65% at a sensitivity of 91%. Multivariate logistic regression analysis showed a significant association between the myosin-11 level and presence of AAA. When the myosin-11 level was combined with hypertension, it improved the prediction of AAA (AUC 0.88) more than hypertension per se. We then investigated the correlation between aortic diameter and circulating myosin-11 levels using AAA serum samples from patients undergoing endovascular aneurysm repair ( n = 20). Circulating myosin-11 levels were significantly correlated with maximum aortic diameter. Furthermore, changes in myosin-11 concentrations from the baseline 12 mo after endovascular aneurysm repair were associated with those in aortic diameter. These data suggest that circulating levels of myosin-11, which is a SMC-specific myosin isoform, may be useful as a biomarker for AAA. NEW & NOTEWORTHY Extensive studies have revealed that inflammation- or proteolysis-related proteins are proposed as biomarkers for abdominal aortic aneurysm (AAA). Changes in these protein concentrations are not specific for smooth muscle, which is a major part of AAA pathologies. Hence, no disease-specific circulating markers for AAA are currently available. We found, using secretome-based proteomic analysis on human AAA tunica media, that myosin heavy chain 11 was associated with AAA. Circulating myosin heavy chain 11 may be a new tissue-specific AAA marker.


Asunto(s)
Aneurisma de la Aorta Abdominal/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Cadenas Pesadas de Miosina/metabolismo , Proteómica/métodos , Anciano , Anciano de 80 o más Años , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/sangre , Aneurisma de la Aorta Abdominal/patología , Biomarcadores/sangre , Estudios de Casos y Controles , Cromatografía Liquida , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Cadenas Pesadas de Miosina/sangre , Espectrometría de Masas en Tándem , Técnicas de Cultivo de Tejidos
7.
Arterioscler Thromb Vasc Biol ; 37(1): 156-165, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27856458

RESUMEN

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease that is associated with persistent inflammation and extracellular matrix degradation. The molecular mechanisms underlying the macrophage-mediated progression of AAA remain largely unclear. APPROACH AND RESULTS: We show that focal adhesion kinase (FAK) expression and activity are enhanced in macrophages that are recruited to AAA tissue. FAK potentiates tumor necrosis factor-α-induced secretion of matrix-degrading enzymes and chemokines by cultured macrophages. FAK also promotes macrophage chemotaxis. In mice, the administration of a FAK inhibitor that tempers local macrophage accumulation markedly suppresses the development and progression of chemically induced AAA. CONCLUSIONS: FAK plays a key role in macrophage behavior, which underlies the chronic progression of AAA. These findings provide insights into AAA progression and identify FAK as a novel therapeutic target.


Asunto(s)
Aorta Abdominal/enzimología , Aneurisma de la Aorta Abdominal/enzimología , Quinasa 1 de Adhesión Focal/metabolismo , Macrófagos/enzimología , Animales , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/prevención & control , Células Cultivadas , Quimiocina CCL2/metabolismo , Quimiotaxis , Modelos Animales de Enfermedad , Activación Enzimática , Quinasa 1 de Adhesión Focal/antagonistas & inhibidores , Humanos , Macrófagos/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/metabolismo , Fosforilación , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal , Factor de Necrosis Tumoral alfa/farmacología
8.
Ophthalmology ; 124(5): 701-708, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28110949

RESUMEN

PURPOSE: To confirm the prophylactic effect of oral acetazolamide against increased intraocular pressure (IOP) in the period immediately after cataract surgery in eyes with primary open-angle glaucoma (POAG) and to evaluate the appropriate administration time of oral acetazolamide to prevent IOP elevation. DESIGN: Randomized clinical study. PARTICIPANTS: Ninety eyes of 90 patients with well-controlled POAG scheduled for phacoemulsification. METHODS: Eyes were assigned randomly to 1 of 3 groups: (1) oral acetazolamide (500 mg) administration 1 hour preoperatively, (2) oral acetazolamide (500 mg) administration 3 hours postoperatively, or (3) no acetazolamide administration. Intraocular pressure was measured using a rebound tonometer 1 hour preoperatively, at the conclusion of surgery (adjusted in the range between 15 and 25 mmHg), and 1, 3, 5, 7, and 24 hours postoperatively. The incidence of eyes with IOP elevation more than 100% above the preoperative IOP was compared. MAIN OUTCOME MEASURES: Postoperative IOP and incidence of eyes with marked IOP elevation. RESULTS: Mean IOP 1 hour preoperatively and that at the conclusion of surgery did not differ significantly among groups. In all groups, mean IOP was significantly elevated from 3 to 7 hours postoperatively, and then decreased at 24 hours. At 1 and 3 hours postoperatively, mean IOP was significantly lower in the group receiving oral acetazolamide preoperatively than in the other 2 groups (postoperative administration or no administration; P ≤ 0.0031). At 5, 7, and 24 hours postoperatively, the IOP was significantly lower in both the preoperative and postoperative administration groups than in the nonadministration group (P ≤ 0.0224). Intraocular pressure elevation of more than 100% occurred in 1 eye (3.3%) in the preoperative administration group, 7 eyes (23.3%) in the postoperative administration group, and 8 eyes (26.6%) in the nonadministration group; the incidence was significantly lower in the preoperative administration group (P = 0.0459). CONCLUSIONS: Eyes with POAG experienced short-term IOP elevation from 3 to 7 hours after phacoemulsification. Oral acetazolamide administration 1 hour preoperatively significantly reduced the IOP elevation from 1 to 24 hours, while administration 3 hours postoperatively reduced the IOP elevation at 5 hours or more after surgery.


Asunto(s)
Acetazolamida/administración & dosificación , Catarata/complicaciones , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Presión Intraocular/efectos de los fármacos , Hipertensión Ocular/prevención & control , Facoemulsificación/efectos adversos , Complicaciones Posoperatorias/prevención & control , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de Anhidrasa Carbónica/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Glaucoma de Ángulo Abierto/complicaciones , Humanos , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Hipertensión Ocular/epidemiología , Hipertensión Ocular/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos
9.
Arterioscler Thromb Vasc Biol ; 35(1): 127-36, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25378412

RESUMEN

OBJECTIVE: Abdominal aortic aneurysm (AAA) is considered a chronic inflammatory disease; however, the molecular basis underlying the sterile inflammatory response involved in the process of AAA remains unclear. We previously showed that the inflammasome, which regulates the caspase-1-dependent interleukin-1ß production, mediates the sterile cardiovascular inflammatory responses. Therefore, we hypothesized that the inflammasome is a key mediator of initial inflammation in AAA formation. APPROACH AND RESULTS: Apoptosis-associated speck-like protein containing a caspase recruitment domain is highly expressed in adventitial macrophages in human and murine AAA tissues. Using an established mouse model of AAA induced by continuous infusion of angiotensin II in Apoe(-/-) mice, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency in Apoe(-/-) mice were shown to decrease the incidence, maximal diameter, and severity of AAA along with adventitial fibrosis and inflammatory responses significantly, such as inflammatory cell infiltration and cytokine expression in the vessel wall. NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency in Apoe(-/-) mice also reduced elastic lamina degradation and metalloproteinase activation in the early phase of AAA formation. Furthermore, angiotensin II stimulated generation of mitochondria-derived reactive oxygen species in the adventitial macrophages, and this mitochondria-derived reactive oxygen species generation was inhibited by NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency. In vitro experiments revealed that angiotensin II stimulated the NLRP3 inflammasome activation and subsequent interleukin-1ß release in macrophages, and this activation was mediated through an angiotensin type I receptor/mitochondria-derived reactive oxygen species-dependent pathway. CONCLUSIONS: Our results demonstrate the importance of the NLRP3 inflammasome in the initial inflammatory responses in AAA formation, indicating its potential as a novel therapeutic target for preventing AAA progression.


Asunto(s)
Angiotensina II , Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/metabolismo , Inflamasomas/metabolismo , Activación de Macrófagos , Macrófagos/metabolismo , Mitocondrias/metabolismo , Estrés Oxidativo , Anciano , Animales , Aorta Abdominal/inmunología , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/inmunología , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/prevención & control , Apolipoproteínas E , Proteínas Reguladoras de la Apoptosis/deficiencia , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Adaptadoras de Señalización CARD , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Caspasa 1/deficiencia , Caspasa 1/genética , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Fibrosis , Humanos , Inflamasomas/genética , Inflamasomas/inmunología , Mediadores de Inflamación/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/inmunología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Factores de Tiempo
10.
Graefes Arch Clin Exp Ophthalmol ; 254(3): 505-13, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26816295

RESUMEN

PURPOSE: The aim of this study was to examine the recent status of intraocular lens (IOL) dislocation according to a classification system based on vertical dislocation position, as well as the surgical techniques and outcomes of IOL exchange surgery. METHODS: The medical records of 230 eyes from 214 consecutive patients who experienced IOL dislocation and underwent exchange surgery between 2006 and 2014 were reviewed. Vertical dislocation sites observed preoperatively under operating microscopy were examined, along with the surgical techniques and outcomes of IOL exchange. RESULTS: Dislocation sites included (1) the anterior chamber (12.2 %), (2) pseudophakodonesis (19.1 %), (3) the anterior vitreous cavity (47.4 %), (4) trap door-like dislocation (dangling in the peripheral vitreous cavity; 16.1 %), and (5) the retinal surface (5.2 %). The IOL retained in the anterior segment was moved onto the iris by pulling it up through the limbal side ports with an anterior vitrectomy (67.8 %), or by pushing it up from the pars plana with an anterior vitrectomy (26.5 %), while the IOL dropped on the retina was lifting it up from the retina after pars plana vitrectomy (5.7 %). Mean uncorrected and distance-corrected visual acuity significantly improved postoperatively (p < 0.0001). Major complications included a marked elevation in intraocular pressure (7.8 %), pupillary capture (6.5 %), and vitreous hemorrhage (2.6 %). CONCLUSIONS: Based on the classification system, approximately 95 % of dislocated IOLs were retained in the anterior segment, and these IOLs were exchanged using an anterior approach through limbal incisions with an anterior vitrectomy. Visual acuity improved significantly, and serious complications were uncommon, probably because the IOL exchange techniques were standardized and simplified without pars plana vitrectomy.


Asunto(s)
Migracion de Implante de Lente Artificial/clasificación , Implantación de Lentes Intraoculares , Lentes Intraoculares , Facoemulsificación , Adulto , Anciano , Anciano de 80 o más Años , Segmento Anterior del Ojo/patología , Migracion de Implante de Lente Artificial/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Vitrectomía
11.
Int J Mol Sci ; 16(5): 11213-28, 2015 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-25993292

RESUMEN

HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (statins) have been suggested to attenuate abdominal aortic aneurysm (AAA) growth. However, the effects of statins in human AAA tissues are not fully elucidated. The aim of this study was to investigate the direct effects of statins on proinflammatory molecules in human AAA walls in ex vivo culture. Simvastatin strongly inhibited the activation of nuclear factor (NF)-κB induced by tumor necrosis factor (TNF)-α in human AAA walls, but showed little effect on c-jun N-terminal kinase (JNK) activation. Simvastatin, as well as pitavastatin significantly reduced the secretion of matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-2 and epithelial neutrophil-activating peptide (CXCL5) under both basal and TNF-α-stimulated conditions. Similar to statins, the Rac1 inhibitor NSC23766 significantly inhibited the activation of NF-κB, accompanied by a decreased secretion of MMP-9, MCP-2 and CXCL5. Moreover, the effect of simvastatin and the JNK inhibitor SP600125 was additive in inhibiting the secretion of MMP-9, MCP-2 and CXCL5. These findings indicate that statins preferentially inhibit the Rac1/NF-κB pathway to suppress MMP-9 and chemokine secretion in human AAA, suggesting a mechanism for the potential effect of statins in attenuating AAA progression.


Asunto(s)
Aneurisma de la Aorta Abdominal/patología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Transducción de Señal/efectos de los fármacos , Simvastatina/farmacología , Anciano , Anciano de 80 o más Años , Aminoquinolinas/farmacología , Antracenos/farmacología , Aorta Abdominal/efectos de los fármacos , Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/metabolismo , Quimiocina CCL8/metabolismo , Quimiocina CXCL5/metabolismo , Humanos , Técnicas In Vitro , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Pirimidinas/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Proteína de Unión al GTP rac1/antagonistas & inhibidores , Proteína de Unión al GTP rac1/metabolismo
12.
J Surg Res ; 183(1): 472-7, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23295196

RESUMEN

BACKGROUND: The precise pathologic mechanisms underlying human thoracic aortic aneurysms (TAAs) remain uncertain, except that matrix metalloproteinase-9 (MMP-9) is considered a key enzyme for the degradation of extracellular matrix in aneurysm walls. The aim of this study was to elucidate the significance of the angiotensin II (AngII) pathway to MMP-9 production in human TAA walls. METHODS AND RESULTS: We examined the activation of Smad2, a common downstream molecule of AngII and transforming growth factor ß (TGF-ß) pathways, and the expression of MMP-9 in human nonsyndromic TAA walls. We observed significant increases in Smad2 activation and MMP-9 expression, associated with disruption of elastic lamellae. Using human TAA walls in ex vivo culture, we investigated whether AngII and/or TGF-ß pathways are essential for MMP-9 production. Unexpectedly, TGF-ß receptor inhibitor had no effect on MMP-9 production. We used PD98059, an inhibitor of extracellular signal-regulated kinase (ERK) activation, and demonstrated that PD98059 dramatically reduced MMP-9 production with attenuation of Smad2 activation. Moreover, exogenous AngII resulted in increases in Smad2 activation and MMP-9 production, in an ERK-dependent manner. CONCLUSION: Our findings indicate that the AngII/ERK pathway has an important role in the production of MMP-9 in human nonsyndromic TAA walls.


Asunto(s)
Angiotensina II/metabolismo , Aneurisma de la Aorta Torácica/enzimología , Metaloproteinasa 9 de la Matriz/metabolismo , Proteína Smad2/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas , Regulación hacia Arriba
13.
Arterioscler Thromb Vasc Biol ; 32(6): 1410-7, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22499992

RESUMEN

OBJECTIVE: The mechanisms underlying abdominal aortic aneurysm development remain unknown. We hypothesized that acceleration of glucose metabolism with the upregulation of glucose transporters is associated with abdominal aortic aneurysm development. METHODS AND RESULTS: Enhanced accumulation of the modified glucose analogue 18 fluoro-deoxyglucose by positron emission tomography imaging in the human abdominal aortic aneurysm was associated with protein expressions of glucose transporters-1 and -3, assessed by Western blot. The magnitude of glucose transporter-3 expression was correlated with zymographic matrix metalloproteinase-9 activity. Intraperitoneal administration of glycolysis inhibitor with 2-deoxyglucose significantly attenuated the dilatation of abdominal aorta induced by periaortic application of CaCl(2) in C57BL/6J male mice or reduced the aneurysmal formation in angiotensin II-infused apolipoprotein E knockout male mice. In monocytic cell line induced by phorbol 12-myristate 13-acetate or ex vivo culture obtained from human aneurysmal tissues, 2-deoxyglucose abrogated the matrix metalloproteinase-9 activity and interleukin-6 expression in these cells/tissues. Moreover, 2-deoxyglucose attenuated the survival/proliferation of monocytes and the adherence of them to vascular endothelial cells. CONCLUSIONS: This study suggests that the enhanced glycolytic activity in aortic wall contributes to the pathogenesis of aneurysm development. In addition, pharmacological intervention in glycolytic activity might be a potential therapeutic target for the disorder.


Asunto(s)
Aorta Abdominal/efectos de los fármacos , Aneurisma de la Aorta Abdominal/prevención & control , Desoxiglucosa/administración & dosificación , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Glucólisis/efectos de los fármacos , Angiotensina II , Animales , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/genética , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Western Blotting , Cloruro de Calcio , Adhesión Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 3/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Inyecciones Intraperitoneales , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Tomografía de Emisión de Positrones , Radiofármacos/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Factores de Tiempo , Células U937 , Regulación hacia Arriba
14.
Arterioscler Thromb Vasc Biol ; 32(6): 1400-9, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22556334

RESUMEN

OBJECTIVE: Recently, we reported that angiopoietin-like protein 2 (Angptl2) functions in various chronic inflammatory diseases. In the present study, we asked whether Angptl2 and its associated chronic inflammation contribute to abdominal aortic aneurysm (AAA). METHODS AND RESULTS: Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl(2)-induced AAA mouse model. When Angptl2-deficient mice were used in the mouse model, they showed decreased AAA development compared with wild-type mice, as evidenced by reduction in aneurysmal size, less severe destruction of vessel structure, and lower expression of proinflammatory cytokines and matrix metalloproteinase-9. However, no difference in the number of infiltrating macrophages within the aortic aneurysmal vessel wall was observed between genotypes. AAA development was also significantly suppressed in wild-type mice that underwent Angptl2-deficient bone marrow transplantation. Expression levels of proinflammatory cytokines and metalloproteinase-9 in Angptl2-deficient macrophages were significantly decreased, and those decreases were rescued by treatment of Angptl2 deficient macrophages with exogenous Angptl2. CONCLUSIONS: Macrophage-derived Angptl2 contributes to AAA development by inducing inflammation and degradation of extracellular matrix in the vessel wall, suggesting that targeting the Angptl2-induced inflammatory axis in macrophages could represent a new strategy for AAA therapy.


Asunto(s)
Angiopoyetinas/metabolismo , Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/metabolismo , Macrófagos/metabolismo , Proteína 2 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Angiopoyetinas/deficiencia , Angiopoyetinas/genética , Animales , Aorta Abdominal/inmunología , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/genética , Aneurisma de la Aorta Abdominal/inmunología , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/prevención & control , Trasplante de Médula Ósea , Cloruro de Calcio , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Matriz Extracelular/metabolismo , Regulación de la Expresión Génica , Genotipo , Humanos , Inmunohistoquímica , Mediadores de Inflamación/metabolismo , Macrófagos/inmunología , Macrófagos/patología , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo
15.
Br J Ophthalmol ; 107(7): 920-926, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35301217

RESUMEN

AIMS: To examine whether long-term corneal astigmatic changes after stabilisation of surgically induced astigmatism (SIA) following cataract surgery differ among eyes having against-the-rule (ATR), with-the-rule (WTR), and oblique astigmatism. METHODS: Anterior corneal astigmatism of 390 eyes in 390 patients (130 eyes each having ATR, WTR and oblique astigmatism) who underwent phacoemulsification with a horizontal clear corneal or scleral incision and 390 eyes in 390 control patients without surgery were examined using an auto-keratometer on the day that SIA stabilised (baseline) and at ≥8 years post baseline. Changes in corneal astigmatism during the ≥8 years post baseline were decomposed to vertical/horizontal (Rx) and oblique astigmatism components (Ry), and compared among baseline types of astigmatism and between eyes with and without surgery. RESULTS: The mean corneal astigmatic changes (Rx and Ry) showed an ATR shift of 0.2-0.3 D during the ≥8 years post baseline, which did not differ significantly among the ATR, WTR and oblique astigmatism groups in eyes with and without surgery. In the ATR, WTR and oblique groups, the mean Rx and Ry did not differ significantly between eyes with and without surgery. Double angle plots revealed an equivalent degree of ATR change in the ATR, WTR and oblique groups between eyes with and without surgery. CONCLUSION: Long-term corneal astigmatic changes towards ATR astigmatism occurred to a similar extent in eyes having ATR, WTR, oblique astigmatism and were comparable between eyes with and without surgery, suggesting that astigmatism type need not be considered when planning astigmatism correction.


Asunto(s)
Astigmatismo , Extracción de Catarata , Catarata , Enfermedades de la Córnea , Facoemulsificación , Humanos , Astigmatismo/etiología , Astigmatismo/cirugía , Estudios Retrospectivos , Córnea/cirugía , Enfermedades de la Córnea/cirugía , Catarata/complicaciones , Topografía de la Córnea
16.
Cornea ; 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38049154

RESUMEN

PURPOSE: The purpose of this study was to compare age-related changes in corneal astigmatism in eyes with and without high myopia. METHODS: Eight-hundred eyes with high myopia (axial length ≥26.0 mm) and 800 eyes without high myopia (200 eyes each from patients in their 40s, 50s, 60s, and ≥70s) underwent videokeratographic examination. The amounts of vertical/horizontal (Rx) and oblique astigmatism (Ry) components, irregular astigmatism, and corneal shape were compared between eyes with and without high myopia and among age categories. RESULTS: In both groups, the mean Rx significantly changed to more positive with age (P < 0.001), whereas the Ry did not change significantly. The Rx was significantly more negative in the high myopia group than in the control group in all age categories (P ≤ 0.003), whereas the Ry did not differ significantly. The mean changes in the Rx and Ry during each 2 consecutive decades did not differ significantly between groups. The asymmetry and higher-order irregularity components increased with age (P ≤ 0.001) but did not differ significantly between groups, except for the higher-order irregularity in patients in their 60s (P = 0.018). In the averaged map, the corneal shape changed from with-the-rule to against-the-rule astigmatism with age in both groups, but the changes occurred later in the high myopia group. CONCLUSIONS: Age-related changes from with-the-rule to against-the-rule astigmatism occurred later in eyes with high myopia compared with eyes without high myopia in middle or older aged patients, but this change in each age decade was comparable between eyes with and without high myopia.

17.
Anticancer Res ; 43(8): 3799-3805, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37500143

RESUMEN

BACKGROUND/AIM: Ovarian clear cell carcinoma (CCC) is associated with a poor prognosis and is resistant to chemotherapy. The aim of this study was to investigate the prognosis of CCC in Mie prefecture and to identify poor prognostic factors. PATIENTS AND METHODS: In this multi-center retrospective study, we analyzed the data of patients with CCC between February 2012 and December 2020. Patients were staged according to the International Federation of Gynecology and Obstetrics (FIGO) 2014 system. Statistical analyses were performed using the Kaplan-Meier method and compared between the two groups using the log-rank test. RESULTS: A total of 112 patients were included and the median follow-up time was 48 months. There was no difference in the prognosis between stages IA, IC1, and IC2. For patients at stages IA, IC1, and IC2, there was no difference in progression-free survival (PFS) and overall survival between the adjuvant chemotherapy and no chemotherapy groups. Median postrecurrent survival was 18 and 20 months in the stages I-II and III-IV groups, respectively. Multivariate analysis revealed that positive ascites cytology (p=0.006) was associated with PFS for patients at stages I-II and that the stage (p=0.039) was associated with PFS for patients at stages III-IV. CONCLUSION: Positive ascites cytology was a poor prognostic factor for patients at an early stage of CCC. Postoperative chemotherapy could be omitted for patients in stages IA and IC1. Relapsed patients did not respond to the standard treatment and had a poor prognosis regardless of the primary stage.


Asunto(s)
Neoplasias Ováricas , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Estudios Retrospectivos , Ascitis/etiología , Ascitis/patología , Estadificación de Neoplasias , Citología , Pronóstico , Carcinoma Epitelial de Ovario/patología , Quimioterapia Adyuvante
18.
Nat Med ; 11(12): 1330-8, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16311603

RESUMEN

Abdominal aortic aneurysm (AAA) is a common disease among elderly people that, when surgical treatment is inapplicable, results in progressive expansion and rupture of the aorta with high mortality. Although nonsurgical treatment for AAA is much awaited, few options are available because its molecular pathogenesis remains elusive. Here, we identify JNK as a proximal signaling molecule in the pathogenesis of AAA. Human AAA tissue showed a high level of phosphorylated JNK. We show that JNK programs a gene expression pattern in different cell types that cooperatively enhances the degradation of the extracellular matrix while suppressing biosynthetic enzymes of the extracellular matrix. Selective inhibition of JNK in vivo not only prevented the development of AAA but also caused regression of established AAA in two mouse models. Thus, JNK promotes abnormal extracellular matrix metabolism in the tissue of AAA and may represent a therapeutic target.


Asunto(s)
Antracenos/farmacología , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Aneurisma de la Aorta Abdominal/prevención & control , Matriz Extracelular/metabolismo , Regulación de la Expresión Génica/genética , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Adenoviridae , Animales , Aorta/química , Western Blotting , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Proteínas de la Matriz Extracelular/biosíntesis , Vectores Genéticos , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Análisis por Micromatrices , Extractos de Tejidos/metabolismo
19.
J Cataract Refract Surg ; 48(3): 322-327, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34371512

RESUMEN

PURPOSE: To examine the long-term refractive changes after stabilization of surgically induced changes (SICs) subsequent to cataract surgery. SETTING: Private hospital. DESIGN: Case-control study. METHODS: Manifest refraction of 300 eyes of 300 patients who underwent phacoemulsification and 300 eyes of 300 age-matched and sex-matched patients without surgery was examined the day on which SICs stabilized (baseline) and ≥7 years postbaseline using an autorefractometer. Refraction was divided into 3 components: spherical power (M), vertical/horizontal astigmatism (J0), and oblique astigmatism (J45) using power vector analysis, and the components were compared between the 2 timepoints and between groups. RESULTS: Data of All 600 eyes were collected. In the surgery group, the mean M and J45 did not change significantly between baseline and ≥7 years postbaseline, but the J0 significantly decreased between the 2 timepoints (P < .001), indicating an against-the-rule (ATR) shift. In the nonsurgery group, the mean M significantly increased and J0 significantly decreased between the timepoints (P < .001), whereas J45 did not change significantly. The mean change in M between the 2 timepoints was significantly smaller in the surgery group (P < .001), whereas the changes in J0 and J45 did not differ significantly between the timepoints. CONCLUSIONS: Spherical power did not change and refractive astigmatism significantly changed toward ATR astigmatism during the more than 7-year follow-up after stabilization of SICs in pseudophakic eyes, whereas hyperopic and ATR shifts occurred in phakic eyes, and the astigmatic changes were comparable between pseudophakic and phakic eyes.


Asunto(s)
Astigmatismo , Extracción de Catarata , Catarata , Astigmatismo/cirugía , Estudios de Casos y Controles , Niño , Córnea/cirugía , Humanos , Refracción Ocular
20.
Biomedicines ; 10(12)2022 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-36551822

RESUMEN

Pharmacotherapy for abdominal aortic aneurysm (AAA) can be useful for prevention, especially in people at higher risk, for slowing down AAA progression, as well as for post-surgery adjuvant treatment. Our review focuses on novel pharmacotherapy approaches targeted towards slowing down progression of AAA, known also as secondary prevention therapy. Guidelines for AAA are not specific to slow down the expansion rate of an abdominal aortic aneurysm, and therefore no medical therapy is recommended. New ideas are urgently needed to develop a novel medical therapy. We are hopeful that in the future, pharmacologic treatment will play a key role in the prevention and treatment of AAA.

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