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1.
J Biol Chem ; 288(35): 25109-25118, 2013 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-23861389

RESUMO

Corneal dystrophies are genetic disorders resulting in progressive corneal clouding due to the deposition of amyloid fibrils derived from keratoepithelin, also called transforming growth factor ß-induced protein (TGFBI). The formation of amyloid fibrils is often accelerated by surfactants such as sodium dodecyl sulfate (SDS). Most eye drops contain benzalkonium chloride (BAC), a cationic surfactant, as a preservative substance. In the present study, we aimed to reveal the role of BAC in the amyloid fibrillation of keratoepithelin-derived peptides in vitro. We used three types of 22-residue synthetic peptides covering Leu110-Glu131 of the keratoepithelin sequence: an R-type peptide with wild-type R124, a C-type peptide with C124 associated with lattice corneal dystrophy type I, and a H-type peptide with H124 associated with granular corneal dystrophy type II. The time courses of spontaneous amyloid fibrillation and seed-dependent fibril elongation were monitored in the presence of various concentrations of BAC or SDS using thioflavin T fluorescence. BAC and SDS accelerated the fibrillation of all synthetic peptides in the absence and presence of seeds. Optimal acceleration occurred near the CMC, which suggests that the unstable and dynamic interactions of keratoepithelin peptides with amphipathic surfactants led to the formation of fibrils. These results suggest that eye drops containing BAC may deteriorate corneal dystrophies and that those without BAC are preferred especially for patients with corneal dystrophies.


Assuntos
Amiloide/química , Compostos de Benzalcônio/química , Detergentes/química , Proteínas da Matriz Extracelular/química , Peptídeos/química , Fator de Crescimento Transformador beta/química , Amiloide/síntese química , Amiloide/metabolismo , Compostos de Benzalcônio/efeitos adversos , Compostos de Benzalcônio/farmacologia , Doenças da Córnea/induzido quimicamente , Doenças da Córnea/metabolismo , Doenças da Córnea/patologia , Detergentes/efeitos adversos , Detergentes/farmacologia , Proteínas da Matriz Extracelular/síntese química , Proteínas da Matriz Extracelular/metabolismo , Humanos , Soluções Oftálmicas/efeitos adversos , Soluções Oftálmicas/química , Soluções Oftálmicas/farmacologia , Peptídeos/síntese química , Dodecilsulfato de Sódio/química , Fator de Crescimento Transformador beta/síntese química , Fator de Crescimento Transformador beta/metabolismo
2.
Mod Rheumatol ; 24(3): 471-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24252013

RESUMO

OBJECTIVE: IgG4-related disease (IgG4-RD) is characterized by IgG4-positive plasmacytic infiltration and fibrosis in various organs. Orbital involvement in IgG4-RD includes lacrimal glands, extra-ocular muscles, trigeminal nerve and other parts of the orbit. Immunohistochemical staining is used to diagnose IgG4-RD in patients with orbital inflammation. The purpose of this retrospective study was to clarify the clinicopathological features of IgG4-RD complicated with orbital involvement. METHODS: We examined the clinical features, pathological findings and response to treatment in nine patients with IgG4-RD who underwent orbital tissue biopsy between April 2010 and August 2012 at the University of Tsukuba Hospital. RESULTS: Among the nine patients, eight had dacryoadenitis, one had infraorbital nerve swelling, and another one had IgG4-related orbital inflammation. Involvement of other organs was identified in all patients, including involvement of the salivary glands, lymph nodes, lung, kidney and para-aorta. In all patients, biopsy samples from orbital tissues showed lymphoplasmacytic infiltration and fibrosis, and IgG4-positive/IgG-positive plasmacyte ratio of > 40%. All patients were treated with prednisolone (0.6 mg/kg/day) and responded well in early phase, although relapse was noted in two patients following tapering of prednisolone, evident by swelling of lacrimal glands. CONCLUSION: Patients with IgG4-RD complicated with orbital involvement often present with involvement of other organs. The histopathological findings of orbital tissue match the characteristic features of IgG4-RD. Corticosteroid is effective for orbital and systemic involvement in IgG4-RD.


Assuntos
Doenças Autoimunes/diagnóstico , Oftalmopatias/diagnóstico , Imunoglobulina G/sangue , Órbita/patologia , Idoso , Doenças Autoimunes/sangue , Doenças Autoimunes/patologia , Oftalmopatias/sangue , Oftalmopatias/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Exp Eye Res ; 116: 17-26, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23892278

RESUMO

The sirtuins are a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases that helps regulate the lifespan of diverse organisms. The human genome encodes seven different sirtuins (SIRT1-7), which share a common catalytic core domain but possess distinct N- and C-terminal extensions. Dysfunction of some sirtuins have been associated with age-related diseases, such as cancer, type II diabetes, obesity-associated metabolic diseases, neurodegeneration, and cardiac aging, as well as the response to environmental stress. SIRT1 is one of the targets of resveratrol, a polyphenolic SIRT1 activator that has been shown to increase the lifespan and to protect various organs against aging. A number of animal studies have been conducted to examine the role of sirtuins in ocular aging. Here we review current knowledge about SIRT1 and ocular aging. The available data indicate that SIRT1 is localized in the nucleus and cytoplasm of cells forming all normal ocular structures, including the cornea, lens, iris, ciliary body, and retina. Upregulation of SIRT1 has been shown to have an important protective effect against various ocular diseases, such as cataract, retinal degeneration, optic neuritis, and uveitis, in animal models. These results suggest that SIRT1 may provide protection against diseases related to oxidative stress-induced ocular damage, including cataract, age-related macular degeneration, and optic nerve degeneration in glaucoma patients.


Assuntos
Envelhecimento/metabolismo , Oftalmopatias/metabolismo , Sirtuína 1/metabolismo , Regulação para Cima , Envelhecimento/genética , Animais , Oftalmopatias/genética , Humanos , Sirtuína 1/genética
4.
Jpn J Ophthalmol ; 67(4): 440-447, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37314597

RESUMO

PURPOSE: Timolol maleate (timolol), a ß-receptor blocker, reduces intraocular pressure by decreasing aqueous humor production. Timolol reportedly also protects ganglion cells, decreases aqueous humor outflow facility, and destroys the extracellular matrix in the trabecular meshwork. In this study, we investigated the effects of timolol on cultured human trabecular endothelial cells purchased from ScienCell using next-generation sequencing. STUDY DESIGN: Experimental investigation. METHODS: Total ribonucleic acid (RNA) was extracted after 24 h. More than 100 million RNAs in control and timolol-treated group were sequenced using a next-generation sequencer. The expression of 55,778 RNAs was analyzed. RESULTS: A total of 2,105 genes were significantly upregulated and 2,125 genes were downregulated, after the addition of timolol. VGF nerve growth factor inducible (VGF) (388-fold) had the maximum increase in expression, followed by amphiregulin (333-fold), a member of the epidermal growth factor family. Moreover, the expression of extracellular matrix-degrading enzymes, matrix metalloproteinases (MMPs) 1, 2, 3, 10, 12, and 14, increased. CONCLUSION: Timolol exerts various effects on human trabecular endothelial cells. The increase in MMP expression may contribute to the decrease in the aqueous humor outflow facility.


Assuntos
RNA , Timolol , Humanos , Timolol/farmacologia , RNA/genética , Células Endoteliais , Malha Trabecular , Humor Aquoso/metabolismo , Pressão Intraocular , Análise de Sequência de RNA
5.
J Biol Chem ; 286(12): 10856-63, 2011 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-21300800

RESUMO

Mutations in keratoepithelin are associated with blinding ocular diseases, including lattice corneal dystrophy type 1 and granular corneal dystrophy type 2. These diseases are characterized by deposits of amyloid fibrils and/or granular non-amyloid aggregates in the cornea. Removing the deposits in the cornea is important for treatment. Previously, we reported the destruction of amyloid fibrils of ß(2)-microglobulin K3 fragments and amyloid ß by laser irradiation coupled with the binding of an amyloid-specific thioflavin T. Here, we studied the effects of this combination on the amyloid fibrils of two 22-residue fragments of keratoepithelin. The direct observation of individual amyloid fibrils was performed in real time using total internal reflection fluorescence microscopy. Both types of amyloid fibrils were broken up by the laser irradiation, dependent on the laser power. The results suggest the laser-induced destruction of amyloid fibrils to be a useful strategy for the treatment of these corneal dystrophies.


Assuntos
Amiloide/química , Proteínas da Matriz Extracelular/química , Lasers , Peptídeos/química , Tiazóis/química , Fator de Crescimento Transformador beta/química , Amiloide/metabolismo , Benzotiazóis , Distrofias Hereditárias da Córnea/metabolismo , Distrofias Hereditárias da Córnea/terapia , Proteínas da Matriz Extracelular/metabolismo , Humanos , Terapia a Laser , Microscopia de Fluorescência , Peptídeos/metabolismo , Fator de Crescimento Transformador beta/metabolismo
6.
Graefes Arch Clin Exp Ophthalmol ; 250(7): 1023-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22350059

RESUMO

PURPOSE: To visualize irrigation fluid flow and calculate its velocity distribution in the anterior chamber during phacoemulsification by particle image velocimetry. METHODS: Porcine eyes were fixed in a glass chamber filled with balanced salt solution. An ultrasound handpiece was fixed to the glass chamber, and its tip was inserted into the anterior chamber through a corneal incision. Irrigation fluid was mixed with fluorescein-labeled liposomes as tracer particles. During phacoemulsification without ultrasound, a sheet-like Nd-YAG pulsed laser beam was emitted and moved from the iris plane to the top of the cornea continuously. Images of illuminated liposomes in the anterior chamber were captured at short intervals with a CCD camera, and the velocity distribution of irrigation fluid flow was calculated by particle image velocimetry. RESULTS: By particle image velocimetry, the flow velocity distribution could be calculated in any plane of the anterior chamber. Dynamic flow of the irrigation fluid, ejected from the tip of the ultrasound handpiece and returned to an aspiration port, was visualized clearly in the anterior chamber. The maximum flow velocity in the anterior chamber was 342 ± 131 mm/s. CONCLUSIONS: Particle image velocimetry enabled the visualization of irrigation fluid flow and quantification of its velocity distribution in different planes of the anterior chamber during cataract surgery. These data are essential for evaluating the safety and efficacy of new surgical settings and devices during phacoemulsification.


Assuntos
Acetatos/metabolismo , Câmara Anterior/metabolismo , Hidrodinâmica , Minerais/metabolismo , Soluções Oftálmicas/metabolismo , Facoemulsificação , Cloreto de Sódio/metabolismo , Animais , Combinação de Medicamentos , Corantes Fluorescentes , Lipossomos , Modelos Biológicos , Reologia , Sus scrofa , Irrigação Terapêutica
7.
Jpn J Ophthalmol ; 66(6): 579-589, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36181644

RESUMO

PURPOSE: To gain new insights into the etiology of blepharitis, we investigated the causative bacteria in patients with blepharitis and the effects of 1% azithromycin ophthalmic solution. STUDY DESIGN: A multicenter, prospective observational study. METHODS: After the subjects were diagnosed as having blepharitis they were administered 1% azithromycin ophthalmic solution for up to 14 days. Bacterial cultures and smear microscopic examinations of the eyelid margin were conducted at the initial visit, after administering eye drops, and 1 month after the end of eye drop administration. The minimum inhibitory concentrations (MICs) of azithromycin were measured. RESULTS: At the initial visit, the bacterial morphology determined by smear microscopic examinations coincided with that of strains isolated by culture taken from 22 of 45 patients. All detected bacteria were gram-positive, and Corynebacterium spp., Cutibacterium acnes, Staphylococcus epidermidis, Streptococcus spp., and Enterococcus faecalis were isolated most commonly. Compared with the initial visit the number of isolated strains per eye decreased significantly at 7 days after the start of eye drop administration and 1 month after the end of eye drop administration. The azithromycin MICs were temporarily increased after the start of eye drops but then decreased. CONCLUSION: Our study suggests that in blepharitis pathogenicity is characterized by increased strain numbers and amounts of indigenous bacteria. Administering a 1% azithromycin ophthalmic solution suppresses the number of bacterial strains within 1 month after the end of eye drop administration without increasing drug resistance.


Assuntos
Azitromicina , Blefarite , Humanos , Azitromicina/uso terapêutico , Soluções Oftálmicas , Antibacterianos/uso terapêutico , Resultado do Tratamento , Blefarite/diagnóstico , Blefarite/tratamento farmacológico , Bactérias , Protocolos Clínicos , Estudos Observacionais como Assunto , Estudos Multicêntricos como Assunto
8.
Nat Med ; 9(6): 781-8, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12730690

RESUMO

Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal rat, vascular pruning began centrally and extended peripherally, leaving behind a less dense, smaller-caliber vasculature. The pruning was correlated with retinal vascular expression of intercellular adhesion molecule-1 (ICAM-1) and coincided with an outward-moving wave of adherent leukocytes composed in part of cytotoxic T lymphocytes. The leukocytes adhered to the vasculature through CD18 and remodeled it through Fas ligand (FasL)-mediated endothelial cell apoptosis. In a model of oxygen-induced ischemic retinopathy, this process was exaggerated. Leukocytes used CD18 and FasL to obliterate the retinal vasculature, leaving behind large areas of ischemic retina. In vitro, T lymphocytes isolated from oxygen-exposed neonates induced a FasL-mediated apoptosis of hyperoxygenated endothelial cells. Targeting these pathways may prove useful in the treatment of retinal ischemia, a leading cause of vision loss and blindness.


Assuntos
Isquemia/patologia , Leucócitos/fisiologia , Doenças Retinianas/patologia , Neovascularização Retiniana , Vasos Retinianos/crescimento & desenvolvimento , Vasos Retinianos/patologia , Animais , Antígenos CD34/metabolismo , Apoptose , Antígenos CD18/genética , Antígenos CD18/metabolismo , Antígenos CD2/metabolismo , Adesão Celular , Células Cultivadas , Proteína Ligante Fas , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Isquemia/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Ratos , Ratos Long-Evans , Retina/patologia , Doenças Retinianas/metabolismo , Vasos Retinianos/metabolismo
9.
Int Ophthalmol ; 31(1): 29-31, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20661624

RESUMO

BACKGROUND: Klebsiella pneumoniae endophthalmitis is rare and despite immediate management, visual outcome is generally poor. We report a case of endogenous K. pneumoniae endophthalmitis that was treated successfully. CASE: An 80-year-old woman with a liver abscess was diagnosed at an early stage with endogenous K. pneumoniae endophthalmitis. She underwent par plana vitrectomy and lensectomy within 8 h after the onset of ocular symptoms. Secondary implantation of a sulcus-fixated intra-ocular lens (IOL) was performed 12 months later. Final visual acuity OS was 20/20. CONCLUSIONS: The present case highlights the potential benefit of early and broad vitrectomy with lensectomy in the management of endogenous K. pneumoniae endophthalmitis.


Assuntos
Endoftalmite/cirurgia , Infecções Oculares Bacterianas/cirurgia , Infecções por Klebsiella/cirurgia , Klebsiella pneumoniae , Idoso de 80 Anos ou mais , Endoftalmite/diagnóstico , Endoftalmite/microbiologia , Infecções Oculares Bacterianas/diagnóstico , Feminino , Humanos , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/microbiologia , Cristalino/cirurgia , Vitrectomia
10.
J Exp Med ; 198(3): 483-9, 2003 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-12900522

RESUMO

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF164 increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF164-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF164-deficient (VEGF120/188) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF+/+) controls. In contrast, administration of a VEGFR-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte-mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF164 selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined.


Assuntos
Fatores de Crescimento Endotelial/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Isquemia/metabolismo , Linfocinas/metabolismo , Retina/metabolismo , Neovascularização Retiniana/metabolismo , Animais , Animais Recém-Nascidos , Adesão Celular/fisiologia , Modelos Animais de Doenças , Fatores de Crescimento Endotelial/genética , Fatores de Crescimento Endotelial/imunologia , Feminino , Inflamação , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Isquemia/patologia , Leucócitos/metabolismo , Linfocinas/genética , Linfocinas/imunologia , Masculino , Camundongos , Camundongos Knockout , Monócitos/citologia , Monócitos/fisiologia , Neovascularização Fisiológica , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Ratos , Receptores de Interleucina-2/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Retina/patologia , Neovascularização Retiniana/patologia , Vasos Retinianos , Linfócitos T/fisiologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
11.
Biomed Microdevices ; 12(5): 875-86, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20563753

RESUMO

Microstereolithography (microSL) technology can fabricate complex, three-dimensional (3D) microstructures, although microSL has difficulty producing macrostructures with micro-scale features. There are potentially many applications where 3D micro-features can benefit the overall function of the macrostructure. One such application involves a medical device called a coaxial phacoemulsifier where the tip of the phacoemulsifier is inserted into the eye through a relatively small incision and used to break the lens apart while removing the lens pieces and associated fluid from the eye through a small tube. In order to maintain the eye at a constant pressure, the phacoemulsifier also includes an irrigation solution that is injected into the eye during the procedure through a coaxial sleeve. It has been reported, however, that the impinging flow from the irrigation solution on the corneal endothelial cells in the inner eye can damage these cells during the procedure. As a result, a method for reducing the impinging flow velocities and the resulting shear stresses on the endothelial cells during this procedure was explored, including the design and development of a complex, 3D micro-vane within the sleeve. The micro-vane introduces swirl into the irrigation solution, producing a flow with rapidly dissipating flow velocities. Fabrication of the sleeve and fitting could not be accomplished using microSL alone, and thus, a two-part design was accomplished where a sleeve with the micro-vane was fabricated with microSL and a threaded fitting used to attach the sleeve to the phacoemulsifier was fabricated using an Objet Eden 333 rapid prototyping machine. The new combined device was tested within a water container using particle image velocimetry, and the results showed successful swirling flow with an ejection of the irrigation fluid through the micro-vane in three different radial directions corresponding to the three micro-vanes. As expected, the sleeve produced a swirling flow with rapidly dissipating streamwise flow velocities where the maximum measured streamwise flow velocities using the micro-vane were lower than those without the micro-vane by 2 mm from the tip where they remained at approximately 70% of those produced by the conventional sleeve as the flow continued to develop. It is believed that this new device will reduce damage to endothelial cells during cataract surgery and significantly improve patient outcomes from this procedure. This unique application demonstrates the utility of combining microSL with a macro rapid prototyping technology for fabricating a real macro-scale device with functional, 3D micro-scale features that would be difficult and costly to fabricate using alternative manufacturing methods.


Assuntos
Microtecnologia/métodos , Facoemulsificação/instrumentação , Luz , Viscosidade
12.
Chem Biodivers ; 7(6): 1364-70, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20564555

RESUMO

Transparency is essential for eyes, which serve as cameras. However, decreased transparency caused by accumulation of abnormal proteins is commonly observed especially in elderly people. However, the mechanism of accumulation of abnormal proteins in various ocular diseases is still unclear. In the present study, we investigated the role of D-amino acids in the development of accumulation of abnormal proteins in age-related ocular diseases. Whole eyes with age-related macular degeneration were excised from four patients. Surgical specimens with pinguecula were excised from eight patients, and specimens with climatic droplet keratopathy were excised from three patients. Polyclonal antibody to the D-beta-Asp-containing peptide was prepared. Using the antibody, immunohistochemical localization of D-beta-Asp-containing proteins was determined. In eyes with age-related macular degeneration, accumulation of abnormal proteins was observed between the retinal pigment epithelial cells and Bruch's membrane. The accumulated abnormal proteins were positive for D-beta-Asp-containing peptides. In surgical specimens with pinguecula and climatic droplet keratopathy, abnormal accumulation of proteins seen in the superficial layer of the stroma was positive for D-beta-Asp-containing peptide. The results indicate that development of D-beta-Asp-containing proteins in vivo have a central role in the development of accumulation of abnormal proteins in age-related macular degeneration, pinguecula, and climatic drop-like dystrophy.


Assuntos
Envelhecimento , Ácido D-Aspártico/metabolismo , Oftalmopatias/metabolismo , Proteínas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Anticorpos/imunologia , Lâmina Basilar da Corioide/metabolismo , Lâmina Basilar da Corioide/patologia , Doenças da Córnea/metabolismo , Doenças da Córnea/patologia , Substância Própria/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Masculino , Pessoa de Meia-Idade , Epitélio Pigmentado Ocular/metabolismo , Epitélio Pigmentado Ocular/patologia
13.
Chem Biodivers ; 7(6): 1389-97, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20564552

RESUMO

Prior to the emergence of life, it is believed that only L-amino acids were selected for formation of proteins, and that D-amino acids were eliminated on the primitive Earth. Whilst homochirality is essential for life, recently the occurrence of proteins containing D-beta-aspartyl (Asp) residues from various tissues of elderly subjects has been reported. Here, we discuss the presence of D-beta-Asp-containing proteins in the lens, ciliary body, drusen, and sclera of the eye, skin, cardiac muscle, blood vessels of the lung, chief cells of the stomach, longitudinal and circular muscles of the stomach, and small and large intestines. Since the D-beta-Asp residue occurs through a succinimide intermediate, this isomer may potentially be generated in proteins more easily than initially thought. UV Rays and oxidative stress can accelerate the formation of the D-beta-Asp residue in proteins.


Assuntos
Envelhecimento , Ácido D-Aspártico/química , Proteínas/química , Aminoácidos/metabolismo , Ácido D-Aspártico/metabolismo , Humanos , Cristalino/química , Cristalino/metabolismo , Estresse Oxidativo , Proteínas/metabolismo , Estereoisomerismo , Raios Ultravioleta
14.
Clin Ther ; 42(4): 704-710, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32145905

RESUMO

PURPOSE: Acetaminophen has been increasingly used for the treatment of cancer-related pain in Japan since the revision of the package insert on January 21, 2011. However, high-dose acetaminophen may cause liver injury. The objectives of this study were to investigate the prevalence of liver injury in patients receiving acetaminophen and to identify the risk factors. METHODS: The subjects were patients who were treated with acetaminophen ≥1500 mg/d for ≥4 weeks at Ehime University Hospital between April 2011 and December 2014. Drug-induced liver injury was evaluated by alanine aminotransferase and alkaline phosphatase levels, Naranjo score, and Child-Pugh classification. FINDINGS: A total of 287 of 562 patients were treated for 4 weeks with acetaminophen ≥1500 mg/d. Twenty of 102 patients analyzed had drug-induced liver injury. Multivariate analysis was performed with variables from the results of univariate analysis (sex, age ≥70 years, abnormal alanine aminotransferase and alkaline phosphatase levels, and serious liver disease), and age ≥70 years and serious liver disease were significant risk factors. IMPLICATIONS: The findings from the present observational, single-center study suggest that serious liver disease before administration is an independent risk factor for acetaminophen-induced liver injury.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Antipiréticos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Feminino , Humanos , Japão , Masculino , Fatores de Risco
15.
Graefes Arch Clin Exp Ophthalmol ; 247(7): 989-92, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19151994

RESUMO

PURPOSE: Increased concentration of (1,3)-beta-D-glucan, one of the major components of fungal cell walls, is detected in the serum of systemic fungal infection. In our study, the concentration of (1,3)-beta-D-glucan was measured in the tear fluid of patients with mycotic keratitis. METHODS: Tear fluid was collected from patients with fungal keratitis (n = 4) and bacterial corneal ulcers (n = 4) with or without corneal scraping. In addition, tear fluid was collected from patients without corneal diseases. RESULTS: The concentration of (1,3)-beta-D-glucan in tear fluid collected without corneal scraping was 4.0 +/- 3.5, 5.8 +/- 2.6, 184 +/- 128 pg/ml in the control, bacterial corneal ulcer, and mycotic keratitis samples respectively. The concentration of (1,3)-beta-D-glucan in tear fluid collected after scraping the corneal lesions with a tip of glass capillary was 4.4 +/- 1.3, 8.2 +/- 5.2 and >1,000 pg/ml in the control, bacterial ulcer, and mycotic keratitis samples respectively. CONCLUSIONS: A significant increase in (1,3)-beta-D-glucan was detected in tear samples from patients with mycotic keratitis. Measuring the concentration of (1,3)-beta-D-glucan in tear fluid might be helpful in the diagnosis of mycotic keratitis.


Assuntos
Infecções Oculares Fúngicas/metabolismo , Ceratite/metabolismo , Ceratite/microbiologia , Lágrimas/metabolismo , beta-Glucanas/metabolismo , Úlcera da Córnea/metabolismo , Úlcera da Córnea/microbiologia , Infecções Oculares Bacterianas/metabolismo , Infecções Oculares Fúngicas/diagnóstico , Humanos , Ceratite/diagnóstico , Concentração Osmolar , Proteoglicanas
16.
Graefes Arch Clin Exp Ophthalmol ; 247(4): 549-53, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19043733

RESUMO

INTRODUCTION: The toxicity of conventional formulations of amphotericin B deoxycholate (AmB(DOC)) limits its clinical applications. To reduce the toxicity of AmB(DOC), lipid formulations of amphotericin B (AmB) have been developed and clinically applied. In the present study, we evaluated the ocular toxicity and pharmacokinetics of subconjunctival injection of liposomal AmB. MATERIALS AND METHODS: Subconjunctival injection of either AmB(DOC) (containing 1.5 mg of AmB and 1.2 mg of deoxycholate), deoxycholate (1.2 mg), or liposomal amphotericin B (L-AmB) (containing 1.5 mg of AmB and lipids) was given to white New Zealand rabbits. After 24 hours, toxicities of the drugs were evaluated by slit lamp and histologically. To evaluate the pharmacokinetics of subconjunctival injection of L-AmB, the concentration of the drug in the cornea was evaluated at 4, 12, 24, and 48 hours after subconjunctival injection of L-AmB, with or without corneal epithelial removal. RESULTS: Subconjunctival injection of AmB(DOC) or deoxycholate alone induced severe corneal and conjunctival edema, with necrosis and infiltration of inflammatory cells. In contrast, subconjunctival injection of L-AmB induced only mild inflammation near the injection site. The concentration of AmB injected in eyes with intact corneal epithelium was 4.93-2.49, 0.63-0.31, 0.15-0.07 microg/g at 4, 12, and 24 hours respectively after the injection of L-AmB. When injected in eyes after corneal epithelial removal, the concentration of AmB was 19.7-9.87, 2.49-1.25, and 1.25-0.63 microg/g at 4, 12, and 24 hours after injection respectively CONCLUSIONS: Subconjunctival injection of L-AmB has reduced ocular toxicities and gives satisfactory concentrations in corneal stroma compared with conventional AmB(DOC). Subconjunctival injection of L-AmB will be a choice of treatment for mycotic keratitis.


Assuntos
Anfotericina B/farmacocinética , Anfotericina B/toxicidade , Antifúngicos/farmacocinética , Antifúngicos/toxicidade , Animais , Disponibilidade Biológica , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/metabolismo , Doenças da Túnica Conjuntiva/induzido quimicamente , Doenças da Túnica Conjuntiva/metabolismo , Doenças da Córnea/induzido quimicamente , Doenças da Córnea/metabolismo , Substância Própria/efeitos dos fármacos , Substância Própria/metabolismo , Injeções , Masculino , Coelhos
17.
Nippon Ganka Gakkai Zasshi ; 113(3): 424-42; discussion 443, 2009 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-19348186

RESUMO

Long-term duration of lifestyle-related diseases including diabetes induces various ocular diseases. For this reason, the development of lifestyle-related ocular diseases is closely related to the aging process. In the present study, we tried to reveal the molecular mechanism of lifestyle-related ocular diseases, especially diabetic complications of the eyes, in relation to aging. To unify the molecular mechanisms of diabetic complications and aging changes of the eyes, we focused on two kinds of nonenzymatic post-translational modification products: advanced glycation end products (AGEs) and D-amino acids. We found that the accumulation of proteins rich in AGEs and D-amino acids plays a central role in the development of both diabetic complications and such changes of the eyes as diabetic retinopathy, diabetic keratopathy, pinguecula, spheroidal degeneration of the cornea, and drusen. In addition, decreased function in AGE-modified and D-amino acid-containing proteins is a factor in the development of diabetic complications and aging changes in eyes. In this way, posttranslational changes in molecules and amino acids are important contributing factors in the development of diabetic complications and aging changes in eyes. In conclusion, accumulation of AGE-modified and D-amino acid-containing proteins is the molecular mechanism of both diabetic complications and the aging changes in eyes.


Assuntos
Envelhecimento , Aminoácidos/metabolismo , Retinopatia Diabética/etiologia , Produtos Finais de Glicação Avançada/metabolismo , Processamento de Proteína Pós-Traducional , Animais , Olho/patologia , Humanos , Estilo de Vida
18.
J Cataract Refract Surg ; 45(6): 711-718, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30879719

RESUMO

We developed an injector with a tip that matches the shape of the ciliary sulcus (Ciliary Sulcus Pad Injector) and is used in ciliary sulcus suture fixation of intraocular lenses. The injector is inserted through the corneal incisions and slid along the posterior surface of the iris to the opposite side. When the tip of injector is fitted in the ciliary sulcus, the plunger is pressed, causing the needle to pierce the ciliary sulcus. A suture is inserted in the ciliary sulcus without direct observation. In 91.4% of cases, the needle correctly pierced the ciliary sulcus in a single attempt. The difference between the preoperative expected refractive power and the postoperative spherical equivalent power was -0.63 diopter 6 months after surgery.


Assuntos
Corpo Ciliar/cirurgia , Implante de Lente Intraocular/instrumentação , Técnicas de Sutura/instrumentação , Humanos , Lentes Intraoculares , Masculino , Pessoa de Meia-Idade , Agulhas , Suturas
19.
J Cataract Refract Surg ; 44(10): 1247-1253, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30172566

RESUMO

PURPOSE: To determine the relationship of the anatomic position of tissue surrounding the ciliary sulcus using ultrasound biomicroscopy (UBM) for measurement of ciliary sulcus parameters and the surrounding tissue after intracapsular cataract extraction (ICCE) and determine the correct suture site for intraocular lens (IOL) suture fixation. SETTING: Sugiura Eye Clinic, Asahi General Hospital, Shizouka-ken, Japan. DESIGN: Prospective case series. METHODS: Using UBM, the angle of the ciliary sulcus and several areas of the tissue surrounding the ciliary sulcus were measured from 8 orientations in eyes after ICCE. These measurements and endoscopic observation of the ciliary sulcus indicated the optimum points of needle insertion and needle emergence on the sclera for IOL suture fixation. Endoscopic observation of the ciliary sulcus also showed its shape. RESULTS: The shape of the surrounding tissue of the ciliary sulcus was measured in 16 eyes after ICCE, and endoscopy was used to observe the ciliary sulcus during surgery in 150 eyes. For ab interno ciliary sulcus suture fixation, the correct point of needle emergence on the sclera was 2.5 mm from the posterior surgical limbus when a straight needle was used. For ab externo pars plana suture fixation, the correct point of needle insertion on the sclera was 3.0 mm from the posterior surgical limbus. Endoscopic observation showed that the lower surface of the ciliary sulcus was formed by the fusion of neighboring ciliary processes. CONCLUSION: Knowing the detailed shape of ciliary sulcus will allow for more precise IOL suture fixation.


Assuntos
Corpo Ciliar/anatomia & histologia , Corpo Ciliar/cirurgia , Implante de Lente Intraocular/métodos , Técnicas de Sutura , Idoso , Idoso de 80 Anos ou mais , Extração de Catarata , Corpo Ciliar/diagnóstico por imagem , Endoscopia/métodos , Feminino , Humanos , Masculino , Microscopia Acústica , Agulhas , Estudos Prospectivos , Esclera/diagnóstico por imagem , Suturas
20.
Intern Med ; 57(23): 3445-3449, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29984768

RESUMO

We herein report the case of a patient who developed peripheral neuropathy of the bilateral lower legs that later became complicated with isolated oculomotor nerve disorder and was finally diagnosed as systemic lupus erythematosus (SLE). Based on the findings for oculomotor nerve paralysis and contrast-enhanced magnetic resonance imaging findings for the oculomotor nerve in the prepontine cistern, the isolated oculomotor nerve disorder was considered to be a manifestation of peripheral neuropathy. This oculomotor nerve disorder may contribute to the diagnosis of SLE and can be effectively treated with steroid pulse therapy. Reports of SLE manifesting as isolated oculomotor nerve paralysis are rare.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Doenças do Nervo Oculomotor/etiologia , Doenças do Sistema Nervoso Periférico/etiologia , Anti-Inflamatórios/administração & dosagem , Encéfalo/diagnóstico por imagem , Meios de Contraste , Feminino , Humanos , Extremidade Inferior/inervação , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Imageamento por Ressonância Magnética , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Doenças do Nervo Oculomotor/diagnóstico por imagem , Doenças do Nervo Oculomotor/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Pulsoterapia
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