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1.
Graefes Arch Clin Exp Ophthalmol ; 257(7): 1411-1418, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31119425

RESUMO

PURPOSE: To assess the real-world 5-year treatment outcomes of ranibizumab therapy in Japanese patients with neovascular age-related macular degeneration (AMD). METHODS: This was a retrospective, observational, and open-label effectiveness study that included 295 eyes. The participants were patients with treatment-naïve neovascular AMD who received intravitreal ranibizumab (IVR) monthly injection at least three times as the loading phase, followed by further injections as needed (pro re nata (PRN)) and follow-up assessments for 5 years. Outcomes were determined at least 5 years after the first ranibizumab injection. RESULTS: Mean logMAR best-corrected visual acuity (BCVA) at baseline was 0.52. The mean BCVA significantly improved after three loading injections; however, it declined gradually. The BCVA at 1 year was significantly better than the baseline BCVA, whereas the 3-year, 4-year, and 5-year BCVA values were significantly lower than the baseline values. The average central foveal thickness improved significantly from 366 ± 125 µm to 268 ± 134 µm (p < 0.0001). Macular atrophy was significantly more likely to occur in cases with classic choroidal neovascularization (CNV) than in cases with other AMD (p = 0.01). CONCLUSIONS: IVR is well tolerated in eyes with AMD. However, a PRN regimen for AMD may have limited real-world effectiveness for long-term maintenance of improved visual acuity. Macular atrophy may occur more frequently in classic CNV. To maintain good vision, IVR treatment should be started earlier and performed continuously.


Assuntos
Angiofluoresceinografia/métodos , Macula Lutea/patologia , Ranibizumab/administração & dosagem , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/epidemiologia
2.
PLoS One ; 14(2): e0213161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30818384

RESUMO

PURPOSE: Abnormal fundus autofluorescence (FAF) potentially precedes onset of late age-related macular degeneration (AMD) in Caucasian patients. Many differences exist between Asian and Caucasian patients regarding AMD types and severity, gender, and genetic backgrounds. We investigated the characteristics of abnormal FAF and retinal sensitivity in the fellow eyes of Japanese patients with unilateral neovascular AMD. METHODS: Sixty-six patients with unilateral neovascular AMD and abnormal FAF in the fellow eye were enrolled in this multicenter, prospective, observational study. The best-corrected visual acuity, fundus photographs, FAF images, and retinal sensitivity on microperimetry were measured periodically for 12 months. The FAF images were classified into eight patterns based on the International Fundus Autofluorescence Classification Group. The points measured by microperimetry were superimposed onto the FAF images and fundus photographs and classified as "within," "close," and "distant," based on the distance from the abnormal FAF and other findings. The relationship between the location of the baseline abnormal FAF and retinal sensitivity was investigated. RESULTS: In Japanese patients, patchy (33.3%) and focally increased (30.3%) patterns predominated in the abnormal FAF. Intermediate-to-large drusen was associated predominantly with hyperfluorescence and hypofluorescence. Neovascular AMD developed within 1 year in six (9.1%) eyes, the mean baseline retinal sensitivity of which was 12.8 ± 4.7 dB, significantly (p<0.002) lower than the other eyes. In 44 of the other 60 eyes, microperimetry was measurable at baseline and month 12 and the mean retinal sensitivity improved significantly from 13.5 ± 4.4 to 13.9 ± 4.8 dB (p<0.001), possibly associated with lifestyle changes (e.g., smoking cessation, antioxidant and zinc supplementation). The mean retinal sensitivities of points within and close to the abnormal FAF were 9.9 and 11.7 dB, respectively, which were significantly lower than the 14.0 dB of the points distant from the abnormal FAF. CONCLUSION: In Japanese patients, patchy and focally increased patterns predominated in the abnormal FAF. The retinal sensitivity was lower close to/within the abnormal FAF. FAF and microperimetry are useful to assess macular function before development of neovascular AMD or geographic atrophy.

3.
Chemosphere ; 220: 687-695, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30605811

RESUMO

The ubiquitous environmental obesogens tributyltin (TBT) and perfluorooctane sulfonate (PFOS) may accumulate in parent and be transferred to their offspring, resulting in trans-generational adverse effects. In this study, we investigated the combined toxic and obesogenic effects of TBT and PFOS on the early life stages of Japanese medaka (Oryzias latipes). In ovo nanoinjection was used to simulate the maternal transfer process. Doses were controlled at 0, 0.05, 0.5, and 2.5 ng/egg (TBT) and at 0, 0.05, 0.5, and 5.0 ng/egg (PFOS), with a full factorial design for mixture formulations. Relatively high doses of agents in mixtures were needed to induce significant mortality (TBT ≥ 0.5 ng/egg) or delayed hatching (PFOS = 5.0 ng/egg) of embryos. The interaction between TBT and PFOS in mixtures had significant effects on the observed hatching delay, but not on acute mortality. Compared with controls, separate exposure to TBT (or PFOS) notably elevated adipose areas at the doses of 0.05 and 0.5 ng/egg, but not at the highest doses. Combined exposure significantly promoted the fat accumulation in newly hatched larvae, even when the doses of TBT and PFOS were both at the levels that did not show obesogenic effect. The interactive effect of TBT and PFOS could aggravate the total obesogenic effect of their mixtures, indicating a synergistic interaction. These results highlight the importance of paying close attention to interaction effects when addressing the impacts of mixtures of environmental obesogens.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Ácidos Alcanossulfônicos/farmacologia , Fluorcarbonetos/farmacologia , Oryzias/metabolismo , Compostos de Trialquitina/farmacologia , Tecido Adiposo/crescimento & desenvolvimento , Animais , Sinergismo Farmacológico , Embrião não Mamífero/efeitos dos fármacos , Feminino , Larva/efeitos dos fármacos , Exposição Materna/efeitos adversos , Obesidade/induzido quimicamente , Oryzias/embriologia
4.
Gan To Kagaku Ryoho ; 45(11): 1661-1664, 2018 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-30449859

RESUMO

A 57-year-old female patient received ileocecal colon resection because of colon cancer. Pathological findings showed pSSN2M0(pStage III b). After surgery, CapeOX was administered as an adjuvant chemotherapy. On day 13 of CapeOX treatment, severe oral mucositis and Grade 4 myelosuppression appeared, and the CapeOX treatment was immediately stopped. However, these adverse effects continued for 19 days, and she gradually recovered. The severe myelosuppression was caused bydeficiencyof DPD, which is a keyenzy me that metabolizes 5-FU. While DPD deficiencyis veryrare, we need to consider that 5-FU causes severe adverse events in patients with DPD deficiency.

5.
Toxicon ; 153: 58-61, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30170168

RESUMO

The pufferfish saxitoxin- and tetrodotoxin-binding protein 2 (PSTBP2), which is involved in toxin accumulation, was knocked out in Takifugu rubripes embryos by using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 genome-editing technology. Treating the embryos with one of two single-guide RNA (sgRNA) resulted in mutation rates of 57.1% and 62.5%, respectively, as estimated using a heteroduplex mobility assay at 3 days postfertilization. Both sgRNAs might induced frameshift mutations that knocked out the T. rubripes PSTBP2.

6.
Semin Ophthalmol ; 33(6): 813-819, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30084710

RESUMO

PURPOSE: To estimate the prevalence and risk factors for polypoidal choroidal vasculopathy (PCV) in a general Japanese population. METHODS: This population-based, cross-sectional study was conducted in 2007 with subjects from the Hisayama Study. Of the 3,648 residents in Hisayama, Japan, 2,663 who were ≥ 50 years old were enrolled in this study. The characteristics of PCV were determined by fundus examination or based on indocyanine green and fluorescein angiographic findings. We evaluated the contributions of the risk factors for PCV. RESULTS: Among the 207 participants with age-related macular degeneration (AMD), 174 (6.5%) had early AMD, and 33 (1.2%) had late AMD, including 10 participants with PCV (0.4%). Male and smoking habit were significant risk factors for the development of PCV. CONCLUSIONS: The prevalence of PCV is higher among Japanese subjects than Caucasians in Western countries. Male gender and smoking habit were significant risk factors for PCV in a general Japanese population.


Assuntos
Doenças da Coroide/epidemiologia , Corioide/irrigação sanguínea , Pólipos/epidemiologia , Vigilância da População , Medição de Risco , Distribuição por Idade , Doenças da Coroide/complicações , Doenças da Coroide/diagnóstico , Estudos Transversais , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Japão/epidemiologia , Masculino , Pólipos/diagnóstico , Prevalência , Fatores de Risco , Distribuição por Sexo , Fatores de Tempo , Degeneração Macular Exsudativa/complicações , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/epidemiologia
7.
J Hum Genet ; 63(10): 1083-1091, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30054556

RESUMO

To identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0 × 10-5). Of the candidate genes within these loci, three were relevant to VEGF-related pathway (KCNMA1, SOCS2, and OTX2). The proportions of patients who worsened visual acuity were 13.7%, 38.8%, 58.0%, and 80.0% in patients with 0, 1, 2, and 3 or more identified risk variants, respectively. Changes in visual acuity decreased linearly as the number of risk variants increased (P = 1.67 × 10-12). The area under the curve using age, baseline visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified variants (P < 0.0001). Although further study is needed to confirm their associations, our results offer candidate variants influencing response to ranibizumab therapy.

8.
Environ Sci Pollut Res Int ; 25(25): 25363-25370, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29946846

RESUMO

The present study investigated how principal environmental factors such as temperature and light intensity change the toxicological properties of thiobencarb (TB) herbicide to the green alga, Raphidocelis subcapitata. At first, we investigated the inhibitory effect of TB (0, 15.6, 31.2, 62.4, and 125 µg L-1) on growth of R. subcapitata at five temperatures (10, 15, 20, 25, or 30 °C) for 144 h exposure and calculated 72- and 144-h effective concentration values (EC10, 20, and EC50) for growth rate. All EC values significantly decreased with an increasing temperature. The maximum quantum yield of photosystem II in R. subcapitata exposed to 125 µg L-1 of TB was also significantly inhibited with increased temperature. These physiological effects could explain the lower EC values at high temperatures. Then, single and interactive effects of TB, temperature, and light intensity on growth rate were investigated by three-way of analysis of variance. As a result, single and interactive effects were detected in all explanatory variables. These results suggest that temperature and light intensity change the acute toxicity parameter in R. subcapitata exposed to TB and must be considered in evaluating the risk of TB.

9.
Ophthalmologica ; 239(2-3): 94-102, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29316563

RESUMO

OBJECTIVE: To examine the relationship between early response to anti-vascular endothelial growth factor (VEGF) treatment and visual prognosis. METHODS: We retrospectively separated 20 patients with persistent diabetic macular edema (DME) into two responder status groups based on the reduction of central macular thickness (CMT) from baseline to month 3: a delayed responder group (DRG) (≤25% CMT reduction, n = 11) and an immediate responder group (IRG) (>25% CMT reduction, n = 14). We also separated the patients into two responder status groups based on the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA): a visual nonimprovement group (VNIG) (≥0 logMAR BCVA improvement, n = 11) and a vi sual improvement group (VIG) (<0 logMAR BCVA improvement, n = 14). Finally, we assessed the correlations between logMAR BCVA changes from baseline to month 3 (ΔBCVAM3) and those from baseline to month 12 (ΔBCVAM12). RESULTS: At month 12, BCVA was significantly more improved in the VIG than the VNIG (p < 0.005), but was not significantly different between the DRG and the IRG (p = 0.75). The Pearson correlation coefficient showed a significant relationship between ΔBCVAM3 and ΔBCVAM12 (r = 0.60, p < 0.005). CONCLUSIONS: BCVA showed significantly greater improvement in the VIG than in the VNIG. ΔBCVAM3 may predict the visual outcome at month 12 in DME patients treated with anti-VEGF drugs.


Assuntos
Bevacizumab/administração & dosagem , Edema Macular/tratamento farmacológico , Acuidade Visual , Idoso , Inibidores da Angiogênese/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Macula Lutea/patologia , Edema Macular/etiologia , Masculino , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento
10.
Br J Ophthalmol ; 102(8): 1047-1053, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29146756

RESUMO

AIMS: To evaluate the prevalence of and factors associated with age-related macular degeneration (AMD) in a rural population of southwestern Japan. METHODS: This population-based cross-sectional study of all residents aged 40 years or older was conducted on the island of Kumejima, Okinawa, Japan. Of 4632 eligible residents, 3762 completed a comprehensive questionnaire and underwent ocular examination (participant rate, 81.2%). A non-mydriatic fundus photograph was used to grade AMD lesions according to the Wisconsin protocol. Prevalence of AMD was calculated and factors associated with AMD were identified by logistic regression. RESULTS: Of 3068 subjects with gradable photographs, 469 had early AMD and 4 had late AMD. Age-adjusted prevalence was 13.4% for any AMD, 13.3% for early AMD and 0.09% for late AMD. In multivariate analysis, any AMD was positively associated with age (OR 1.04 per year, 95% CI 1.03 to 1.05), male sex (OR 1.42, 95% CI 1.14 to 1.75) and history of cataract surgery (OR 1.35, 95% CI 1.00 to 1.82) and was negatively associated with longer axial length (OR 0.85 per millimetre, 95% CI 0.74 to 0.96). Early AMD similarly showed significant associations with these same factors. CONCLUSIONS: Prevalence of early or late AMD in a southwestern island population of Japan was 13.4% or 0.09%. Our data suggest relatively high prevalence for early AMD and low prevalence for late AMD in this sample of rural Japanese population. Significant factors associated with any or early AMD were mostly similar to that of previous studies.

11.
Environ Sci Pollut Res Int ; 25(2): 1551-1558, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29098580

RESUMO

Distribution of perfluorooctane sulfonate (PFOS) was investigated in tissues (plasma, blood clot, mucus, skin, liver, muscle, and gonad) of tiger puffer fish Takifugu rubripes. A single dose of PFOS was intraperitoneally injected at 0.1 mg/kg body weight with samples taken over a 14-day period. The highest concentration of PFOS was found in the plasma, 861 ng/mL at 14 days, followed by the mucus, liver, blood clot, gonads, muscles, and skin of fish. A gradual upward trend in PFOS concentration was observed in the mucus and liver whereas there was no change in the plasma, blood clot, gonad, muscle, and skin after the initial increase in PFOS concentrations following injection. No significant trend for estimated total PFOS content in whole body was observed during the experimental period. Relatively high concentrations of PFOS (690 ng/g ww after 14 days) were detected in body surface mucus that continuously oozes from the skin. These results may suggest that mucus is one of the elimination pathways of PFOS in tiger puffer fish.


Assuntos
Ácidos Alcanossulfônicos/farmacocinética , Fluorcarbonetos/farmacocinética , Muco/metabolismo , Takifugu/metabolismo , Ácidos Alcanossulfônicos/administração & dosagem , Ácidos Alcanossulfônicos/análise , Animais , Fluorcarbonetos/administração & dosagem , Fluorcarbonetos/análise , Fígado/metabolismo , Distribuição Tecidual
12.
Clin Ophthalmol ; 11: 1697-1705, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29033535

RESUMO

BACKGROUND: Pars plana vitrectomy is the only treatment for advanced proliferative diabetic retinopathy (PDR). However, vitrectomy is not always successful despite current progress in vitreoretinal surgical techniques. The aim of our study was to investigate whether the vitreal concentrations of MCP-1, IL-6, IL-8, and VEGF are elevated after unsuccessful vitrectomy in patients with PDR and to investigate whether the altered levels of these cytokines are associated with the cause for the reoperation. PATIENTS AND METHODS: Vitreous samples were collected from 263 eyes of 233 patients: PDR (n=129 eyes), proliferative vitreoretinopathy (PVR; n=24 eyes) and nondiabetic controls (n=110 eyes) prior to vitrectomy. Vitreous samples were also collected from 14 eyes of 14 patients with PDR before vitrectomy and from the same 14 eyes before a second vitrectomy for reoperation. The levels of MCP-1, IL-6, IL-8, and VEGF were measured by flow cytometry using a cytometric bead array (CBA) assay. RESULTS: The mean concentrations of vitreal MCP-1, IL-6, IL-8, and VEGF were significantly higher in patients with PDR and PVR (P<0.01). There were significantly high correlations among the concentrations of MCP-1, IL-6, and IL-8, whereas the correlation of VEGF with the other 3 cytokines was lower. Among the 14 patients who required reoperation, the mean vitreal concentrations of MCP-1, IL-6, and IL-8 were higher than that at the time of the initial vitrectomy (P<0.01). At the time of the reoperation vitrectomy, the mean vitreous level of MCP-1, IL-6, and IL-8 in eyes with fibrous proliferation was higher than in those without fibrous proliferation (P<0.05). In contrast, VEGF in eyes with neovascular glaucoma (NVG) or anterior hyaloidal fibrovascular proliferation (AHFVP) was higher than in the eyes without NVG and AHFVP (P<0.05). CONCLUSION: The elevated levels of MCP-1, IL-6, and IL-8 may be the cause of the postoperative fibrous proliferation. In contrast, VEGF may be the cause of the neovascularization after unsuccessful vitrectomy in the eyes of PDR patients.

13.
Aquat Toxicol ; 192: 148-154, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28957716

RESUMO

Although most exposures to chlorpyrifos (CPF) in natural flowing waters are brief and episodic, there have been a few reports of the persistence of abnormal fish behaviors caused by such acute exposure. The present study focused on the behavioral and biochemical responses of Japanese medaka (Oryzias latipes) to acute, sublethal exposure to CPF, as well as the persistence of the effects during a 3-week recovery test in CPF-free water. The medaka became hyperactive and exhibited an elevated anxiety state after a 4-day exposure to 0.024mg/L of CPF, but they recovered from these abnormal behavioral responses within 7days of recovery treatment. In contrast, persistent impacts on some startle responses to a sudden stimulation (induced by a ball drop) were observed in medaka exposed to CPF. The reaction latency did not change immediately after the 4-day exposure, but was significantly prolonged by as much as 21days after the termination of exposure. The post-stimulus swimming distance within 5s significantly decreased on the day immediately after the 4-day exposure, but it significantly increased after 7days of recovery treatment. The activity of acetylcholinesterase (AChE) in the brains of medaka was significantly inhibited on the day immediately after the 4-day exposure, but it returned to 80% and 110% of that in control fish on days 7 and 21 of the recovery period, respectively. However, AChE activities in the eyes of exposed medaka were persistently inhibited and declined to 33%, 71%, and 72% of that in control fish on days 0 (immediately after the 4-day exposure), 7, and 21 of recovery, respectively. Correlation analysis suggested that the changes of AChE activities in the brains of medaka may underlie some of the observed acute behavioral changes, and the changes of AChE activities in the eyes may contribute to the persistence of the abnormalities in the reaction latency of the startle response. Our findings suggest that medaka need a long time to recover from acute, sublethal exposure to CPF, and the persistence of the behavioral abnormalities might affect their fitness in natural habitats.


Assuntos
Ansiedade/fisiopatologia , Comportamento Animal/efeitos dos fármacos , Clorpirifos/toxicidade , Locomoção/efeitos dos fármacos , Oryzias/fisiologia , Reflexo de Sobressalto/efeitos dos fármacos , Testes de Toxicidade Aguda , Acetilcolinesterase/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Olho/efeitos dos fármacos , Olho/enzimologia , Natação , Poluentes Químicos da Água/toxicidade
14.
Sci Total Environ ; 607-608: 367-374, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-28697389

RESUMO

Organisms in natural environments are often exposed to a broad variety of chemicals, and the multi-chemical mixtures exposure may produce significant toxic effects, even though the individual chemicals are present at concentrations below their no-observed-effect concentrations. This study represents the first attempt that uses the accelerated failure time (AFT) model to quantify the interaction and toxicity of multi-chemical mixtures in environmental toxicology. We firstly conducted the acute immobilization tests with Daphnia magna exposed to mixtures of diazinon (DZN), fenitrothion (MEP); and thiobencarb (TB) in single, binary, and ternary formulations, and then fitted the results to the AFT model. The 48-h EC50 (concentration required to immobilize 50% of the daphnids at 48h) values for each pesticide obtained from the AFT model are within a factor of 2 of the corresponding values calculated from the single pesticide exposure tests, indicating the methodology is able to provide credible toxicity values. The AFT model revealed either significant synergistic (DZN and MEP; DZN and TB) or antagonistic (MEP and TB) interactions in binary mixtures, while the interaction pattern of ternary mixture depended on both the concentration levels and concentration ratios of pesticides. With a factor of 2, the AFT model accurately estimated the toxicities for 78% of binary mixture formulations that exhibited significant synergistic effects, and the toxicities for all the ternary formulations. Our results showed that the AFT model can provide a simple and efficient way to quantify the interactions between pesticides and to assess the toxicity of their mixtures. This ability may greatly facilitate the ecotoxicological risk assessment of exposure to multi-chemical mixtures.


Assuntos
Daphnia/efeitos dos fármacos , Praguicidas/toxicidade , Animais , Diazinon/toxicidade , Fenitrotion/toxicidade , Tiocarbamatos/toxicidade , Testes de Toxicidade
15.
Ophthalmologica ; 238(3): 163-171, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28697497

RESUMO

PURPOSE: To evaluate 1-year outcomes of intravitreal injections of aflibercept (IVA) in Japanese polypoidal choroidal vasculopathy (PCV) patients. METHODS: In this prospective, open-label, single-arm multicenter clinical trial, treatment-naïve PCV patients received IVA (2.0 mg) every 2 months, after 3 initial monthly doses. The primary endpoint assessed was the proportion of patients maintaining baseline best-corrected visual acuity (BCVA) at 1 year. RESULTS: Fifty eyes with PCV were included in the study. BCVA was maintained or improved in 97.6% of the patients. Mean logMAR BCVA at baseline was 0.33, and had improved to 0.12 logMAR 1 year after the initiation of aflibercept treatment (p < 0.001). Mean central foveal thickness decreased from 356 to 239 µm (p < 0.001). Complete regression of polypoidal lesions was seen in 72.5% after 1 year of treatment. CONCLUSIONS: One year of IVA resulted in stabilization of BCVA and anatomical improvement in Japanese PCV patients.


Assuntos
Doenças da Coroide/tratamento farmacológico , Corioide/irrigação sanguínea , Pólipos/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Acuidade Visual , Idoso , Idoso de 80 Anos ou mais , Corioide/patologia , Doenças da Coroide/diagnóstico , Doenças da Coroide/epidemiologia , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Incidência , Injeções Intravítreas , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pólipos/diagnóstico , Pólipos/epidemiologia , Estudos Prospectivos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fatores de Tempo , Tomografia de Coerência Óptica , Resultado do Tratamento
16.
Ecotoxicol Environ Saf ; 145: 78-82, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28708984

RESUMO

Chlorpyrifos (CPF) is one of the most widely used insecticides and has been found in both urban and rural water bodies. In this study, we studied variations in the social behavioral patterns, swimming behavior, and brain acetylcholinesterase (AChE) activity of Japanese medaka exposed to lethal (0.12mg/L) and sublethal (0.012mg/L) concentrations of CPF after different exposure times. Group behavior performance (schooling, shoaling, and solitary) was determined on day 4 of lethal exposure and on days 4, 8, and 12 of sublethal exposure. Swimming speed and brain AChE activity were measured on days 4, 8, 12, 16, and 20 of sublethal CPF exposure. We observed significant decreases in social behavior and swimming speed (i.e., hypoactivity) in fish exposed to lethal CPF concentrations for 4 days. At the sublethal concentration, there was increased schooling duration and hyperactivity of fish on day 8 but not on day 4. In contrast, 12 days of sublethal CPF exposure resulted in social behavior responses similar to those after 4 days' lethal exposure, i.e., significant decreases in schooling frequency and duration with a notable increase in duration of solitary behavior. Brain AChE activity was inhibited in a time-dependent manner. Altered fish behavior in response to organophosphorus pesticides such as CPF may be mediated by more than AChE inhibition alone.


Assuntos
Comportamento Animal/efeitos dos fármacos , Clorpirifos/toxicidade , Oryzias/fisiologia , Comportamento Social , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Relação Dose-Resposta a Droga , Natação , Fatores de Tempo
17.
Exp Ther Med ; 13(6): 3509-3515, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28587434

RESUMO

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) images show significant contrast for cancer tissues against non-cancerous tissues. Fusion of a DWIBS and a T2-weighted image (DWIBS/T2) can be used to obtain functional, as well as anatomic, information. In the present study, the performance of DWIBS/T2 in the diagnosis of abdominal solid cancer was evaluated. The records of 14 patients were retrospectively analyzed [5 patients with hepatocellular carcinoma (HCC), 4 with metastatic liver cancer, 3 with pancreatic cancer, 1 with renal cellular carcinoma and 1 with malignant lymphoma of the para-aortic lymph node]. T1WI and T2WI scans did not detect pancreatic cancer in certain cases, whereas DWIs and DWIBS/T2 clearly demonstrated pancreatic cancer in all cases. In addition, metastatic liver cancer and HCC were successfully detected with abdominal US and CECT; however, US did not detect pancreatic cancer in 1 case, while CECT and DWIBS/T2 detected pancreatic cancer in all cases. In conclusion, the diagnostic performance of DWIBS/T2 was the same as that of abdominal US and CECT in detecting primary and metastatic liver cancer. DWIBS/T2 enabled the diagnosis of pancreatic cancer in cases where it was not detected with US, T1WI or T2WI.

18.
Chemosphere ; 181: 530-535, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28463727

RESUMO

This study is the first to report sound production in Japanese medaka (Oryzias latipes). Sound production was affected by exposure to the carbamate insecticide (aldicarb) and heavy-metal compound (copper sulfate). Medaka were exposed at four concentrations (aldicarb: 0, 0.25, 0.5, and 1 mg L-1; copper sulfate: 0, 0.5, 1, and 2 mg L-1), and sound characteristics were monitored for 5 h after exposure. We observed constant average interpulse intervals (approx 0.2 s) in all test groups before exposure, and in the control groups throughout the experiment. The average interpulse interval became significantly longer during the recording periods after 50 min of exposure to aldicarb, and reached a length of more than 0.3 s during the recording periods after 120 min exposure. Most medaka fish stopped to produce sound after 50 min of exposure to copper sulfate at 1 and 2 mg L-1, resulting in significantly declined number of sound pulses and pulse groups. Relative shortened interpulse intervals of sound were occasionally observed in medaka fish exposed to 0.5 mg L-1 copper sulfate. These alternations in sound characteristics due to toxicants exposure suggested that they might impair acoustic communication of medaka fish, which may be important for their reproduction and survival. Our results suggested that using acoustic changes of medaka has potential to monitor precipitate water pollutions, such as intentional poisoning or accidental leakage of industrial waste.


Assuntos
Aldicarb/farmacologia , Sulfato de Cobre/farmacologia , Oryzias/fisiologia , Som , Animais , Monitoramento Ambiental/métodos , Inseticidas/farmacologia , Reprodução , Poluentes Químicos da Água/farmacologia
19.
Bull Environ Contam Toxicol ; 99(1): 131-137, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28401255

RESUMO

To provide an overview of anthropogenic contaminants in liquid organic fertilizers (LOFs), products from four biogas plants in Kyushu, Japan, were analyzed for a wide range of contaminants, including copper, cadmium, tributyltin (TBT), dibutyltin (DBT), perfluorooctane sulfonate, 952 semi-volatile organic compounds, and 89 antibiotics. The highest concentrations of copper (31.1 mg/L) and cadmium (0.08 mg/L) were found in LOFs from the Hita biogas plant. Only ofloxacin and sulfapyridine were detected in total 89 antibiotics screened. TBT, DBT, and perfluorooctane sulfonate were present at low concentrations in the LOFs from all four locations. Among the 952 semi-volatile organic compounds, 78 compounds were detected in at least one sample and were present at concentrations between 1.2 and 139.6 mg/L. On the basis of comparisons with previous studies and quality standards for the use of organic fertilizers, the concentrations of contaminants in the studied LOFs indicate that they might be safe for agricultural purposes.


Assuntos
Agricultura/métodos , Fertilizantes/análise , Poluentes do Solo/análise , Ácidos Alcanossulfônicos/análise , Cádmio/análise , Monitoramento Ambiental , Fluorcarbonetos/análise , Japão , Compostos Orgânicos de Estanho/análise , Plantas , Compostos de Trialquitina/análise
20.
Mol Med Rep ; 15(6): 3949-3956, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28440413

RESUMO

Choroidal neovascularization (CNV) is a serious complication of age­related macular degeneration. The aim of the present study was to investigate the expression and distribution of M1 and M2 macrophages in a laser­induced CNV adult mouse model. The mRNA expression levels of M1, M2 and pan macrophage markers, and macrophage­associated angiogenic cytokines, were determined by reverse transcription­quantitative polymerase chain reaction. Immunofluorescence studies were performed to determine the location of the macrophages. The expression levels of M1 macrophage markers increased to a greater extent compared with M2 markers in the retinal pigment epithelium (RPE)­choroid complexes following laser photocoagulation. By contrast, the expression levels of M2 macrophage markers increased primarily in the retinas. Immunofluorescence studies revealed that the increased number of cluster of differentiation (CD)206­positive cells were located primarily in the retina, whereas the CD80­positive cells were located around the site of CNVs in the RPE­choroid. In addition, the M1­associated cytokines increased to a greater extent in the RPE­choroid complexes, whereas the M2­associated cytokines were highly expressed in the retinas. These findings indicate that M1 and M2 macrophage numbers increased following CNV; however, the locations were different in this mouse model of laser­induced CNV. The results of the present study suggest that M1 macrophages have a more direct role in inhibiting the development of CNV.


Assuntos
Neovascularização de Coroide/etiologia , Neovascularização de Coroide/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Biomarcadores , Quimiotaxia de Leucócito/genética , Quimiotaxia de Leucócito/imunologia , Neovascularização de Coroide/patologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Macrófagos/patologia , Degeneração Macular/complicações , Masculino , Camundongos , Retina/imunologia , Retina/metabolismo , Retina/patologia
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