Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Diagn Cytopathol ; 52(2): E54-E58, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38031825

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in adults occurring in a background of cirrhosis. Peritoneal dissemination of HCC is an unusual presentation with an incidence of 2%-16%. Peritoneal metastasis of an unruptured HCC is extremely uncommon. Despite low yield, ascitic fluid cytology serves as a valuable tool for diagnostic evaluation in a patient of cirrhosis with suspicion of malignant transformation. We present a rare case scenario in an elderly female with cirrhosis where the diagnosis of peritoneal metastasis was established on ascitic fluid cytology and confirmed by immunocytochemistry. This report illustrates the unique clinical presentation of an unruptured HCC with its cytological features and a brief review of literature.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Peritoneais , Idoso , Feminino , Humanos , Líquido Ascítico/patologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Citologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia
2.
Sci Rep ; 13(1): 19744, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957159

RESUMO

The fabrication of a Poly (vinylidene fluoride) membrane (PVDF) and ceramic-assisted bismuth vanadate-polyvinylidene fluoride (BiVO4-PVDF) composite membrane was achieved through the utilization of the electrospinning technique. The composition and structure of the fabricated membranes were characterized by X-ray powder diffraction, Raman analysis, scanning electron microscopy, Thermo gravimetric analyzer, Fourier transform infrared spectroscopy, and UV-Vis spectroscopy techniques. The prepared polymeric membranes were then utilized for catalytic investigation and to explore, how structure affects catalytic activity using 5 mg/L, 10 mL methylene blue (MB) dye solution. Ultrasonication, visible light irradiation, and the combination were used to study piezocatalysis, photocatalysis, and piezo-photocatalysis, moreover, degradation intermediates were also explored using scavengers. Electrospun BiVO4-PVDF (BV-PVDF) composite has been found to have better piezocatalytic and photocatalytic properties than PVDF. The experimental findings reveal that the composite of BiVO4-PVDF demonstrates the highest efficiency in dye degradation, achieving a maximum degradation rate of 61% within a processing time of 180 min. The rate of degradation was calculated to be 0.0047 min-1, indicating a promising potential for the composite in the field of dye degradation.

4.
Materials (Basel) ; 16(16)2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37630001

RESUMO

Ferroelectric materials are known to possess multicatalytic abilities that are nowadays utilized for removing organic pollutants from water via piezocatalysis, photocatalysis, piezo-photocatalysis, and pyrocatalysis processes. The Ba0.85Ca0.15Ti0.9Zr0.1O3 (BCZTO) ceramic is one such ferroelectric composition that has been extensively studied for electrical and electronic applications. Furthermore, the BCZTO ceramic has also shown remarkable multicatalytic performance in water-cleaning applications. The present review explores the potentiality of BCZTO for water-cleaning and bacterial-killing applications. It also highlights the fundamentals of ferroelectric ceramics, the importance of electric poling, and the principles underlying piezocatalysis, photocatalysis, and pyrocatalysis processes in addition to the multicatalytic capability of ferroelectric BCZTO ceramic.

5.
Glob Chall ; 7(2): 2200122, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36778779

RESUMO

In the present numerical simulation work, effective elastic and piezoelectric properties are calculated and a comparative study is conducted on a cement matrix-based piezocomposite with 0-3 and gyroid triply periodic minimal surface (TPMS) inclusions. The present study compares the effective properties of different piezoelectric materials having two different types of connectivity of the inclusions namely, 0-3 inclusions where the inclusions are physically separated from each other and are embedded within the matrix and the second one is TPMS inclusions having interpenetrating phase type connectivity. Effective properties are calculated for four different materials at five different volume fractions namely, 10%, 15%, 20%, 25%, and 30% volume fractions of inclusion by volume. In terms of effective properties and direct piezoelectric effect, TPMS piezocomposite is found to perform better compared to 0-3 piezocomposite. Lead-free piezoelectric material 0.5Ba(Ca0.8Zr0.2)O3 - 0.5(Ba0.7Ca0.3)TiO3 demonstrates better performance compared to all other material inclusions studied. The present study attempts to highlight improved piezoelectric effective properties of lead-free material-based piezocomposites with TPMS inclusions.

6.
Dialogues Health ; 3: 100146, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38515797

RESUMO

Background: For primary healthcare systems to bring care closer to the communities, the availability of appropriate human resources is crucial. The primary care workforce in the world is expanding to include non-physician health workers (NPHWs) to increase its capacity. Also, NPHWs as mid-level health providers (MLHPs) are currently being employed in high- and low-income countries to assist doctors and specialists to make up for the scarcity of health professionals. Given the wide prevalence in the deployment of NPHWs as mid-level health providers, this article collates recent evidence on the role of MLHPs in improving access to primary healthcare services, and their enablers and barriers in integrating them in primary care teams. The article also presents gaps in evidence and recommendations for the way forward. Methods: A systematic search of contemporary literature published from January 2012 to September 2022 was undertaken using two bibliographic databases (PubMed and Cochrane) and hand searching the reference list of retrieved papers. Duplicates, papers older than ten years, and whose focus was not on primary healthcare were excluded. The papers finalised for appraisal were scrutinised for key themes and their summaries were collated for analysis. The papers comprised of twenty-four quantitative, twenty-three qualitative, and nine mixed approach study designs (n = 56) due to which a narrative approach was conducted as per guidelines. Results: The review identified and presents the following themes - task shifting and its effectiveness in service delivery, quality of care, enablers and barriers of NPHWs in primary health care in both HIC and LMIC settings. Conclusion: Task-shifting interventions need effective engagement and constant coordination with relevant stakeholders. For this, policymakers, public health researchers, healthcare professionals of all cadres and community members need to be involved across all stages of introduction and absorption of the cadre into the primary healthcare delivery system.

7.
Sci Rep ; 12(1): 22610, 2022 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-36585424

RESUMO

Finite element studies were conducted on 0.5Ba(Zr0.2 Ti0.8) O3-0.5(Ba0.7 Ca0.3)TiO3 (BCZT) piezoelectric particles embedded in polyethylene matrix to create a piezocomposite having a positive and negative Poisson's ratio of -0.32 and 0.2. Polyethylene with a positive Poisson's ratio is referred to as non-auxetic while those with negative Poisson's ratio are referred to as auxetic or inherently auxetic. The effective elastic and piezoelectric properties were calculated at volume fractions of (4%, 8% to 24%) to study their sensing and harvesting performance. This study compared lead-free auxetic 0-3 piezocomposite for sensing and energy harvesting with non-auxetic one. Inherently auxetic piezocomposites have been studied for their elastic and piezoelectric properties and improved mechanical coupling, but their sensing and energy harvesting capabilities and behavior patterns have not been explored in previous literatures. The effect of Poisson's ratio ranging between -0.9 to 0.4 on the sensing and energy harvesting performance of an inherently auxetic lead free piezocomposite composite with BCZT inclusions has also not been studied before, motivating the author to conduct the present study. Auxetic piezocomposite demonstrated an overall improvement in performance in terms of higher sensing voltage and harvested power. The study was repeated at a constant volume fraction of 24% for a range of Poisson's ratio varied between -0.9 to 0.4. Enhanced performance was observed at the extreme negative end of the Poisson's ratio spectrum. This paper demonstrates the potential improvements by exploiting auxetic matrices in future piezocomposite sensors and energy harvesters.


Assuntos
Polietileno , Titânio , Fenômenos Físicos
8.
Materials (Basel) ; 15(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36431702

RESUMO

Ferroelectric materials with a spontaneous polarization are proven to be potential multicatalysts in water remediation applications. The composition of 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Sr0.3)TiO3 (BST-BZT) was examined for photocatalysis, piezocatalysis, and piezo-photocatalysis processes by degrading an azo dye named methylene blue (MB). Generally, dis-aligned dipoles restrict the catalytic activities due to which the BST-BZT powder sample was poled by the corona poling technique. Coupled piezocatalysis and photocatalysis process, i.e., the piezo-photocatalysis process has shown maximum dye degradation. There was a significant improvement in degradation efficiency by using a poled BST-BZT sample compared to the unpoled sample in all processes, thus the results suggest an extensive scope of poled ferroelectric ceramic powder in the catalysis field.

10.
Expert Rev Respir Med ; 15(10): 1367-1375, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34227439

RESUMO

OBJECTIVES: To study the histopathology of patients dying of COVID-19 using post-mortem minimally invasive sampling techniques. METHODS: This was a single-center observational study conducted at JPNATC, AIIMS. Thirty-seven patients who died of COVID-19 were enrolled. Post-mortem percutaneous biopsies were taken from lung, heart, liver, kidney and stained with hematoxylin and eosin. Immunohistochemistry was performed using CD61 and CD163. SARS-CoV-2 virus was detected using IHC with primary antibodies. RESULTS: The mean age was 48.7 years and 59.5% were males. Lung histopathology showed diffuse alveolar damage in 78% patients. Associated bronchopneumonia was seen in 37.5% and scattered microthrombi in 21% patients. Immunopositivity for SARS-CoV-2 was observed in Type II pneumocytes. Acute tubular injury with epithelial vacuolization was seen in 46% of renal biopsies. Seventy-one percent of liver biopsies showed Kupffer cell hyperplasia and 27.5% showed submassive hepatic necrosis. CONCLUSIONS: Predominant finding was diffuse alveolar damage with demonstration of SARS-CoV-2 protein in the acute phase. Microvascular thrombi were rarely identified in any organ. Substantial hepatocyte necrosis, Kupffer cell hypertrophy, microvesicular, and macrovesicular steatosis unrelated to microvascular thrombi suggested that liver might be a primary target of COVID-19.


Assuntos
COVID-19 , Autopsia , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Centros de Atenção Terciária
11.
J Adv Prosthodont ; 13(2): 79-88, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34025956

RESUMO

PURPOSE: To assess peri-implant stress distribution using finite element analysis in implant supported fixed partial denture with occlusal schemes of cuspally loaded occlusion and implant protected occlusion. MATERIALS AND METHODS: A 3-D finite element model of mandible with D2 bone with partially edentulism with unilateral distal extension was made. Two Ti alloy identical implants with 4.2 mm diameter and 10 mm length were placed in the mandibular second premolar and the mandibular second molar region and prosthesis was given with the mandibular first molar pontic. Vertical load of 100 N and and oblique load of 70 N was applied on occlusal surface of prosthesis. Group 1 was cuspally loaded occlusion with total 8 contact points and Group 2 was implant protected occlusion with 3 contact points. RESULTS: In Group 1 for vertical load , maximum stress was generated over implant having 14.3552 Mpa. While for oblique load, overall stress generated was 28.0732 Mpa. In Group 2 for vertical load, maximum stress was generated over crown and overall stress was 16.7682 Mpa. But for oblique load, crown stress and overall stress was maximum 22.7561 Mpa. When Group 1 is compared to Group 2, harmful oblique load caused maximum overall stress 28.0732 Mpa in Group 1. CONCLUSION: In Group 1, vertical load generated high implant stress, and oblique load generated high overall stresses, cortical stresses and crown stresses compared to vertical load. In Group 2, oblique load generated more overall stresses, cortical stresses, and crown stresses compared to vertical load. Implant protected occlusion generated lesser harmful oblique implant, crown, bone and overall stresses compared to cuspally loaded occlusion.

12.
Appl Radiat Isot ; 166: 109327, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32768922

RESUMO

Over years, soil radon (Rn-222) measurement was started at Multi-parametric Geophysical Observatory (MPGO), Ghuttu, Garhwal Himalaya to assess the earthquake precursory signatures. We carried out a statistical analysis to examine anomalous soil radon emanation during the occurrence of local earthquakes. Twenty earthquakes of moderate and bigger magnitude are occurred within 300 km from MPGO, Ghuttu during 2009-2017. Continuous time series highlight a high effect of rainfall precipitation on the soil radon emanation measured at 10 m depth. During monsoon period (June to September), high rain precipitation at the recording site cause a high variation in the radon emanation. In spite of our best efforts, it is difficult to isolate the complex behavior of heavy and abrupt occurrence of rain from the soil radon data. Preferably, the data of 11 events of the pre- and post-monsoon are evaluated to identify the seismic origin effect on soil radon. To examine these anomalous variations, statistical analysis of soil radon data is carried out by calculating mean (m), and then obtaining standard deviation (σ) from mean values. Changes in the soil radon concentration are treated anomalous for values exceeding one and two standard deviations (m±σ and m±2σ) from the mean value for the selected duration. Two nearby and the strongest events suggests pre-seismic variations which are related to the earthquake precursory signatures. The observed results are explained in the light of dilatancy- diffusion model.

13.
Glob Chall ; 2(1): 1700084, 2018 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31565302

RESUMO

This study proposes the design of a micro-spiral-shaped piezoelectric energy harvester that scavenges energy from blood pressure variation in the cardiac cycle. The harvester can be a miniaturized perennial source of power that could even eliminate the need for replacement of conventional batteries used in current pacemaker technology. The concept of a 25 µm thin spiral-based piezoelectric energy harvester with a diameter of 6 mm satisfying the dimensional constraints has been proposed. A number of lead-free materials have been used along with Pb[Zr x Ti1- x ]O3 (PZT-5A) to compare the performance. The harvester has been designed in such a way that the natural frequency of the structure remains in the range of 1.1-1.3 Hz, which is equivalent to 66-78 heart beats min-1 of humans. The obtained alternating electric current from piezoelectric materials is converted into direct current. The maximum open-circuit voltage obtained is ≈0.9 V, which is not sufficient for charging a pacemaker battery. Therefore, boost converter circuit is employed to step up the voltage. It is found that K0.475Na0.475Li0.05(Nb0.92Ta0.05Sb0.03)O3 (KNLNTS) has the best performance as compared to other materials under study. The boosted voltage obtained from KNLNTS is ≈6 and ≈7 V for 80 and 90% duty cycle, respectively, which are sufficient for pacemaker battery charging.

14.
J Clin Diagn Res ; 11(3): MD01-MD03, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28511419

RESUMO

Nasal Natural Killer (NK)/T cell lymphoma, commonly mentioned in the literature as Lethal Midline Granuloma (LMG) is an unusual pathology of the oro-maxillo-facial region characterized by aggressive and progressive destruction of the face, nose, palate and pharynx. This disease is now classified as a T-cell lymphoma based on modern cytogenetics, immunologic and molecular studies. However, it is mentioned in various literatures by various names. Here, we present one such clinically diagnosed, histopathologically and immunologically confirmed case of LMG, designated as NK/T cell lymphoma in a 56-year-old male. The uncommon presentation of NK/T cell lymphomas should be kept as a differential diagnosis for management of patients.

15.
Am Heart J ; 170(3): 543-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26385038

RESUMO

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) have been shown to reduce morbidity and mortality in patients with heart failure (HF) with reduced ejection fraction but are associated with hyperkalemia. We sought to evaluate the frequency, variation, and predictors associated with serum potassium monitoring in patients with HF initiated on an MRA among facilities in the Veterans Affairs (VA) Health Care System. METHODS: We performed a retrospective cohort analysis of patients with HF across 133 Veterans Affairs facilities from 2003 to 2013 who were given a new prescription of an MRA. The primary outcome was the mean percentage of patients per facility with serum potassium monitoring within 14 days of MRA dispensing. Univariate and covariate analyses were performed to determine factors associated with monitoring. RESULTS: There were 142,880 patients identified with HF initiated on an MRA who met the study inclusion and exclusion criteria. The mean (SD) percentage of patients per facility with serum potassium monitoring within 14 days was 41.6% (standard deviation 8.0%; minimum 18.9%, maximum 56.7%). Facilities with a higher frequency of monitoring were associated with membership in the Council on Teaching Hospitals (n = 70, P < .0001), had academic affiliations (n = 100, P < .0001), and a higher annual volume of patients with HF (≥200 patients, P < .0001). CONCLUSIONS: In a large multicenter national sample of patients with HF receiving a new MRA prescription, the frequency of serum potassium monitoring was below recommended guidelines. Academic facilities and those with a higher volume of patients with HF were associated with an increased frequency of monitoring.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Hiperpotassemia/sangue , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Potássio/sangue , United States Department of Veterans Affairs/estatística & dados numéricos , Idoso , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Hospitalização , Humanos , Hiperpotassemia/epidemiologia , Hiperpotassemia/etiologia , Incidência , Masculino , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
16.
J Indian Prosthodont Soc ; 15(3): 237-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26929519

RESUMO

CONTEXT: To fully estimate the burden of illness due to edentulism and establish valid treatment outcomes measures in this regard, it is equally important to study its psychosocial repercussions. AIMS: The aim was to conduct a study to explore the emotional reactions to tooth loss, screen for current depressive symptoms and test for association between the two; among an edentulous Gujarati population. SETTINGS AND DESIGN: A total of 147 edentulous people visiting the Prosthodontics Department were surveyed. SUBJECTS AND METHODS: A questionnaire (based on previous studies) to test the emotional reactions to tooth loss and Nine Item-Patient Health Questionnaire to test for depression were used. STATISTICAL ANALYSIS USED: The data were analyzed using the Chi-square (χ (2)) test with the help of SPSS v. 18.0 (IBM Corp., Armonk, NY, USA). RESULTS: Totally, 100 out of 147 edentulous people returned the questionnaire of which 58% experienced difficulties in accepting tooth loss and 37% felt unprepared for its effects. Those with difficulties accepting tooth loss had a greater effect on self esteem and social life, had more reservation about discussing tooth loss and was more likely to experience depression. Both groups were satisfied with dentures, had no problem meeting their friends or partners without dentures and leaving out dentures at night. CONCLUSION: About 58% of edentulous people had difficulties accepting tooth loss, which was unrelated to denture satisfaction. Respondents appeared to be restricted in social activities mainly due to functional limitations. Those with difficulties accepting tooth loss were more likely to experience depression.

17.
J Contemp Dent Pract ; 15(2): 242-9, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25095851

RESUMO

Maxillary necrosis can occur due to bacterial infections such as osteomyelitis, viral infections, such as herpes zoster or fungal infections, such as mucormycosis, aspergillosis etc. Mucormycosis is an opportunistic fungal infection, which mainly infects immunocompromised patients. Once the maxilla is involved, surgical resection and debridement of the necrosed areas can result in extensive maxillary defects. The clinician is to face many a challenge in order to replace not only the missing teeth, but also the lost soft tissues and bone, including hard palate and alveolar ridges. The prosthesis (Obturator) lacks a bony base and the lost structures of the posterior palatal seal area compromise retention of the prosthesis. Furthermore, the post surgical soft tissues are scarred and tense, which exert strong dislodging forces. The present article describes the prosthetic rehabilitation of maxillary necrosis secondary to mucormycosis in two cases, one completely edentulous and the other partially edentulous.


Assuntos
Planejamento de Prótese Dentária , Doenças Maxilares/microbiologia , Mucormicose/cirurgia , Obturadores Palatinos , Adulto , Técnica de Moldagem Odontológica , Retenção em Prótese Dentária , Planejamento de Dentadura , Retenção de Dentadura , Prótese Total Superior , Prótese Parcial Removível , Feminino , Seguimentos , Humanos , Arcada Edêntula/reabilitação , Arcada Parcialmente Edêntula/reabilitação , Maxila/cirurgia , Doenças Maxilares/reabilitação , Doenças Maxilares/cirurgia , Seio Maxilar/cirurgia , Pessoa de Meia-Idade , Mucormicose/reabilitação , Fístula Bucoantral/reabilitação , Fístula Bucoantral/cirurgia , Osteomielite/microbiologia , Osteomielite/reabilitação , Osteomielite/cirurgia , Palato Duro/cirurgia , Satisfação do Paciente , Resultado do Tratamento
19.
J Neurochem ; 121(1): 146-56, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22220722

RESUMO

All-trans-retinal and its condensation-products can cause retinal degeneration in a light-dependent manner and contribute to the pathogenesis of human macular diseases such as Stargardt's disease and age-related macular degeneration. Although these toxic retinoid by-products originate from rod and cone photoreceptor cells, the contribution of each cell type to light-induced retinal degeneration is unknown. In this study, the primary objective was to learn whether rods or cones are more susceptible to light-induced, all-trans-retinal-mediated damage. Previously, we reported that mice lacking enzymes that clear all-trans-retinal from the retina, ATP-binding cassette transporter 4 and retinol dehydrogenase 8, manifested light-induced retinal dystrophy. We first examined early-stage age-related macular degeneration patients and found retinal degenerative changes in rod-rich rather than cone-rich regions of the macula. We then evaluated transgenic mice with rod-only and cone-like-only retinas in addition to progenies of such mice inbred with Rdh8(-/-) Abca4(-/-) mice. Of all these strains, Rdh8(-/-) Abca4(-/-) mice with a mixed rod-cone population showed the most severe retinal degeneration under regular cyclic light conditions. Intense light exposure induced acute retinal damage in Rdh8(-/-) Abca4(-/-) and rod-only mice but not cone-like-only mice. These findings suggest that progression of retinal degeneration in Rdh8(-/-) Abca4(-/-) mice is affected by differential vulnerability of rods and cones to light.


Assuntos
Diferenciação Celular , Degeneração Macular/patologia , Estimulação Luminosa/efeitos adversos , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Bastonetes/patologia , Transportadores de Cassetes de Ligação de ATP/efeitos dos fármacos , Transportadores de Cassetes de Ligação de ATP/genética , Idoso , Idoso de 80 Anos ou mais , Oxirredutases do Álcool/deficiência , Oxirredutases do Álcool/genética , Animais , Diferenciação Celular/fisiologia , Progressão da Doença , Feminino , Humanos , Degeneração Macular/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Células Fotorreceptoras Retinianas Cones/metabolismo , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Células Fotorreceptoras Retinianas Bastonetes/metabolismo
20.
J Biol Chem ; 287(7): 5059-69, 2012 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-22184108

RESUMO

Compromised clearance of all-trans-retinal (atRAL), a component of the retinoid cycle, increases the susceptibility of mouse retina to acute light-induced photoreceptor degeneration. Abca4(-/-)Rdh8(-/-) mice featuring defective atRAL clearance were used to examine the one or more underlying molecular mechanisms, because exposure to intense light causes severe photoreceptor degeneration in these animals. Here we report that bright light exposure of Abca4(-/-)Rdh8(-/-) mice increased atRAL levels in the retina that induced rapid NADPH oxidase-mediated overproduction of intracellular reactive oxygen species (ROS). Moreover, such ROS generation was inhibited by blocking phospholipase C and inositol 1,4,5-trisphosphate-induced Ca(2+) release, indicating that activation occurs upstream of NADPH oxidase-mediated ROS generation. Because multiple upstream G protein-coupled receptors can activate phospholipase C, we then tested the effects of antagonists of serotonin 2A (5-HT(2A)R) and M(3)-muscarinic (M(3)R) receptors and found they both protected Abca4(-/-)Rdh8(-/-) mouse retinas from light-induced degeneration. Thus, a cascade of signaling events appears to mediate the toxicity of atRAL in light-induced photoreceptor degeneration of Abca4(-/-)Rdh8(-/-) mice. A similar mechanism may be operative in human Stargardt disease and age-related macular degeneration.


Assuntos
Distrofias Hereditárias da Córnea/metabolismo , Degeneração Macular/metabolismo , Células Fotorreceptoras de Vertebrados/metabolismo , Retinaldeído/metabolismo , Transdução de Sinais , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Animais , Cálcio/metabolismo , Distrofias Hereditárias da Córnea/genética , Distrofias Hereditárias da Córnea/patologia , Humanos , Inositol 1,4,5-Trifosfato/genética , Inositol 1,4,5-Trifosfato/metabolismo , Luz/efeitos adversos , Degeneração Macular/genética , Degeneração Macular/patologia , Camundongos , Camundongos Knockout , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Células Fotorreceptoras de Vertebrados/patologia , Espécies Reativas de Oxigênio/metabolismo , Receptor Muscarínico M3/genética , Receptor Muscarínico M3/metabolismo , Receptor 5-HT2A de Serotonina/genética , Receptor 5-HT2A de Serotonina/metabolismo , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Fosfolipases Tipo C/genética , Fosfolipases Tipo C/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...