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1.
MicroPubl Biol ; 20242024.
Artigo em Inglês | MEDLINE | ID: mdl-38681673

RESUMO

Genetic screens are valuable for identifying novel genes involved in the regulation of developmental processes. To identify genes associated with cell growth regulation in Drosophila melanogaster , a mutagenesis screen was performed. Undergraduate students participating in Fly-CURE phenotypically characterized the E.4.1 mutant which is associated with rough eyes and antennae overgrowth. Following complementation analysis and subsequent genomic sequencing, E.4.1 was identified as a novel mutant allele of GstE14 , a gene involved in ecdysone biosynthesis important for the timing of developmental events. The abnormal eye and antenna phenotypes observed resulting from the loss of GstE14 suggest its role in tissue growth.

2.
BMJ Open ; 13(5): e070641, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37192795

RESUMO

OBJECTIVE: To ascertain the priorities of research in surgical interventions and aftercare in foot and ankle conditions in adults, from inclusive viewpoints of patients, carers, allied professionals and clinicians, as a collaboration with James Lind Alliance (JLA) Priority Setting Partnership. Setting A UK-based national study organised through British Orthopaedic Foot and Ankle Society (BOFAS). DESIGN: A cross-section of both medical and allied professionals, with patient involvement, submitted their 'top priorities' pertaining to foot and ankle pathology, using both paper and web-based formats, which were synthesised into the primary priorities. Following this, workshop-based reviews were used to determine the top 10 priorities. PARTICIPANTS: Adult patients, carers, allied professionals and clinicians who have experienced or managed foot and ankle conditions in the UK. METHODS: A transparent and well-established process developed by JLA was carried out by a steering group of 16 members. A broad survey was designed and disseminated to the public via clinics, BOFAS meetings and website, JLA platforms and electronic media to establish potential research priority questions. Surveys were analysed and initial questions were categorised and cross-referenced with the literature. Those questions that were out of scope and sufficiently answered by research were excluded. The unanswered questions were ranked by the public via a second survey. The top 10 questions were finalised via an extensive workshop. RESULTS: 472 questions from 198 responders were received from the primary survey. 71% (140) from healthcare professionals, 24% (48) from patients and carers and 5% (10) from other responders. 142 questions were out of scope, leaving 330 questions. These were summarised into 60 indicative questions. Reviewing against current literature, 56 questions were left. From the secondary survey, there were 291 respondents: 79% (230) healthcare professionals and 12% (61) patients and carers. After the secondary survey, the top 16 questions were brought to the final workshop to finalise the top 10 research questions. The top 10 questions were: What are the best outcome measures (ways of assessing the effect of the treatment) after foot and ankle surgery? What treatment is the best for Achilles tendon pain? What is the best treatment (including surgery) for tibialis posterior dysfunction (tendon on the inner side of the ankle), leading to a successful long-term outcome? Should physiotherapy be provided following foot and ankle surgery and is there an optimal amount needed to restore function after foot and ankle surgery? At what stage should a patient with ankle instability (ie, an ankle that keeps giving way) be considered for surgical treatment? How effective are steroid injections in improving pain from arthritis in the foot and ankle? What is the best surgery for bone and cartilage defects in the talus? What is better, ankle fusion or ankle replacements? What is the success of surgical lengthening of the calf muscle in improving forefoot pain? What is the best time to start weight bearing after ankle fusion/replacement surgery? CONCLUSION: Top 10 themes included outcomes following interventions, for example, range of movement, reduction in pain, rehabilitation, which included physiotherapy to optimise post intervention outcomes, rehabilitation and condition-specific treatments. These questions will aid to guide national research into foot and ankle surgery. It will also help national funding bodies to prioritise areas of research interest to improve patient care.


Assuntos
Tornozelo , Pesquisa Biomédica , Adulto , Humanos , Tornozelo/cirurgia , Extremidade Inferior , Avaliação de Resultados em Cuidados de Saúde , Inquéritos e Questionários , Prioridades em Saúde , Dor , Reino Unido
3.
Sci Total Environ ; 808: 152071, 2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-34863765

RESUMO

It is proposed that microplastics discharged from wastewater treatment plants act as a vector of pharmaceuticals. In this study, adsorption of pharmaceuticals to polyethylene microplastics was investigated in municipal wastewater. Pharmaceuticals for study were selected to represent different speciation (anionic, cationic, and neutral) and a range of pH dependant octanol-water distribution coefficients (log DOW). Findings revealed adsorption favoured those in cationic form with the greatest hydrophobicity (e.g., fluoxetine log DOW 2.0 at pH 7.8). Adsorption of anionic pharmaceuticals was restricted due to repulsion with the microplastic's negatively charged surface. Only atorvastatin had any appreciable adsorption due to its comparatively high log DOW value (2.9). Those pharmaceuticals predominantly in neutral form (carbamazepine and ketamine) with log DOW values ≥2.4 had similar adsorption. Freundlich KF values were 3400, 386, 284, 259 and 218 (mg kg-1)(mg L-1)1/n for fluoxetine, propranolol, atorvastatin, ketamine, and carbamazepine, respectively. All pharmaceuticals with log DOW values <1.0 (atenolol, gliclazide, bezafibrate, and ifosfamide) did not adsorb to microplastics, irrespective of their speciation. Changing composition of wastewater (pH, dilution with stormwater and NaCl addition) within the range expected for municipal wastewater had limited influence on adsorption. Pharmaceutical desorption from microplastics was assessed in river water and simulated gastric and intestinal fluids. Solution pH was considered the most important factor for pharmaceutical desorption, influencing both pharmaceutical speciation and microplastic surface charge. Greatest desorption was observed for the cationic pharmaceuticals in gastric fluids due to a reduced surface charge of the microplastics under low pH conditions. Up to 50% desorption of fluoxetine occurred in gastric fluid at 37 °C. These findings show that pharmaceuticals adsorbed to microplastics are 'bioavailable'. However, this is often overlooked as an exposure route to aquatic organisms because water samples are normally pre-filtered prior to chemical analysis.


Assuntos
Preparações Farmacêuticas , Poluentes Químicos da Água , Adsorção , Microplásticos , Plásticos , Polietileno , Águas Residuárias , Poluentes Químicos da Água/análise
4.
Foot Ankle Surg ; 28(5): 635-641, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34340904

RESUMO

BACKGROUND: This study aimed to analyse if union and outcome of Arthroscopic Ankle Arthrodesis (AAA) versus Open Ankle Arthrodesis (OAA) were influenced by the extent of coronal plane deformity and to report if patient related factors influence union. METHODS: A total of 122 ankle arthrodesis procedures were included in the study. These were divided into two groups; Group A (n = 99) with deformity less than 15° and Group B (n = 23) with deformity greater than or equal to 15°. Data was collected on patient demographics, medical comorbidities (smoking, diabetes, obesity) and time to union. Patient reported outcome measures (PROMs) evaluated were Manchester Oxford Foot Questionnaire, EuroQol-5D and EuroQol visual analogue health thermometer (EQ-VAS). RESULTS: The mean follow-up in Group A and B was 74.87 and 89.17 months respectively. The average deformity in Group A was 4.9° for AAA and 5.8° for OAA. In Group B it was 18.9° (maximum 28° varus) for AAA and 22.1° (maximum 41° valgus) for OAA. The overall union rate was 95% in Group A (AAA-94%; OAA-100%; [p = 0.20]) and 87% in Group B (AAA-100%; OAA-67%; [p = 0.02]). Mean time to union was 13.2 weeks in Group A (AAA-13.3 weeks; OAA-12.8 weeks; [p = 0.73]) compared to 12.4 weeks for Group B (AAA-12.9 weeks; OAA-11.8 weeks; [p = 0.56]). Irrespective of the extent of deformity and type of surgery, smokers had a 10 times higher likelihood of non-union (p = 0.03). In Group A, none of the PROMs showed significant difference between AAA and OAA. In Group B, EQ-VAS score reached statistical significance (p = 0.03) in favour of AAA whereas other PROMs showed no difference. CONCLUSION: AAA is reproducible in achieving union in end stage ankle arthritis and good PROMs can be expected even in ankles with larger deformities. Regardless of the type of surgery and extent of deformity, smoking is a significant risk factor for non-union. LEVEL OF EVIDENCE: Level III, retrospective comparative series.


Assuntos
Articulação do Tornozelo , Tornozelo , Articulação do Tornozelo/cirurgia , Artrodese/métodos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
5.
J Investig Med High Impact Case Rep ; 9: 23247096211022484, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34078172

RESUMO

Abetalipoproteinemia (ABL) is a rare recessive condition caused by biallelic loss-of-function mutations in the MTTP gene encoding the microsomal triglyceride transfer protein large subunit. ABL is characterized by absence of apolipoprotein B-containing lipoproteins and deficiencies in fat-soluble vitamins leading to multisystem involvement of which neurological complications are the most serious. We present 3 siblings with ABL who were born to non-consanguineous parents of Filipino and Chinese background. Identical twin boys with long-standing failure to thrive and malabsorption were diagnosed at age 2 years. ABL therapy with vitamins and a specialized diet was initiated, replacing total parenteral nutrition at age 3 years. Their younger sister was diagnosed from a blood sample taken at birth; treatment was instituted shortly thereafter. We observed in the twins reversal and in their sister prevention of ABL systemic features following early implementation of fat restriction and high doses of oral fat-soluble vitamins. A targeted sequencing panel found that each affected sibling is homozygous for a novel MTTP intron 13 -2A>G splice acceptor site mutation, predicted to abolish splicing of intron 13. This variant brings to more than 60 the number of reported pathogenic mutations, which are summarized in this article. The twin boys and their sister are now doing well at 11 and 4 years of age, respectively. This experience underscores the importance of early initiation of targeted specialized dietary and fat-soluble vitamin replacements in ABL.


Assuntos
Abetalipoproteinemia , Abetalipoproteinemia/genética , Pré-Escolar , Humanos , Recém-Nascido , Masculino , Mutação , Irmãos , Nucleotídeos de Timina , Vitamina A
6.
Foot Ankle Int ; 42(4): 464-468, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33106028

RESUMO

BACKGROUND: The objective of this study was to evaluate the medium-term results of corticosteroid injections for Morton's neuroma. METHODS: This was a prospective follow-up study of a previous randomized controlled trial (RCT). Forty-five neuromas in 36 patients were injected with a single corticosteroid injection either with or without ultrasound guidance. As the results of the RCT showed no difference in outcomes between techniques, the data were pooled for the purpose of this study. Questionnaires were sent out and responses were collected via mail or telephone interview. Results were available in 42 out of 45 neuromas. There was a sex split of 68% female/32% male with a mean age of 62.6 years (SD, 12 years). RESULTS: At mean follow-up of 4.8 years (SD, 0.91 years), the original corticosteroid injection remained effective in 36% (n = 16) of the patients. In these cases, the visual analog scale (VAS) pain score (P < .001) and Manchester-Oxford Foot Questionnaire Index (MOxFQ Index) (P = .001) remained significantly better than preintervention scores. The remaining cases underwent either a further injection or surgery. Fifty-five percent of the 11 neuromas that received a second injection continued to be asymptomatic in the medium term. Overall, 44% (n = 20) of the initial cohort underwent surgical excision by the medium-term follow-up. The VAS score, MOxFQ Index, and satisfaction scale score across all groups were not significantly different. CONCLUSION: Corticosteroid injections for Morton's neuroma remained effective in over a third of cases for up to almost 5 years. A positive outcome at 1 year following a corticosteroid injection was reasonably predictive of a prolonged effect from the injection. LEVEL OF EVIDENCE: Level II, prospective comparative study.


Assuntos
Neuroma Intermetatársico , Neuroma , Corticosteroides , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma/tratamento farmacológico , Estudos Prospectivos , Ultrassonografia
7.
J Psychopharmacol ; 34(10): 1112-1118, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32842836

RESUMO

BACKGROUND: Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is often used as first- or second-line therapy for depression in older adults. It can be associated with adverse blood pressure (BP) effects. METHODS: Adults ⩾60 years of age in a current major depressive episode were treated in a protocolized manner with venlafaxine XR; 429 participants were treated for 8-16 weeks with a daily dose up to 300 mg to achieve remission from depression. Cardiac measures included sitting and standing BP and heart rate. RESULTS: Of participants who were normotensive at baseline, 6.5% were found to have elevated BP during the study (1.9% <225 mg/day; 9.8% ⩾225 mg/day). There was no significant change in mean BP in the overall sample, or in the subgroup treated with doses ⩾225 mg/day. Additionally, 20.1% of the participants who did not have orthostatic hypotension at baseline were found to have orthostatic hypotension (16.8% <225 mg/day; 22.4% ⩾225 mg/day). Participants with new-onset orthostatic hypotension were significantly more likely to fall than the other participants. CONCLUSION: A large proportion of older adults treated with venlafaxine experience orthostatic hypotension, putting them at risk for falls. A smaller proportion experience elevated BP. Older patients prescribed venlafaxine, particularly at high doses, should be advised and counseled about these adverse effects.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Hipertensão/induzido quimicamente , Hipotensão Ortostática/induzido quimicamente , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Cloridrato de Venlafaxina/administração & dosagem , Acidentes por Quedas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/epidemiologia , Hipotensão Ortostática/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Cloridrato de Venlafaxina/efeitos adversos
8.
J Clin Orthop Trauma ; 11(3): 406-409, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32405199

RESUMO

Morton's neuroma is a common pathology affecting the forefoot. It is not a true neuroma but is fibrosis of the nerve. This is caused secondary to pressure or repetitive irritation leading to thickness of the digital nerve, located in the third or second intermetatarsal space. The treatment options are: orthotics, steroid injections and surgical excision usually performed through dorsal approach. Careful clinical examination, patient selection, pre-operative counselling and surgical technique are the key to success in the management of this condition.

9.
Foot Ankle Surg ; 26(7): 736-743, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31718949

RESUMO

TITLE: Non-surgical treatment for Morton's neuroma: a systematic review. BACKGROUND: Morton's neuroma (MN) is an entrapment degenerative neuropathy with a strong predilection for the 3rd interdigital web space. The objective of our study was to identify the most significant evidence produced for the non-operative treatment of Morton's neuroma and assess outcomes of these interventions. METHOD: The electronic databases Medline, Ovid EMBASE, CINAHL and Cochrane CENTRAL from inception to October 2018 were searched. Two independent reviewers assessed the quality of the studies using the Modified Coleman Criteria. Statistics were combined across cohort studies to calculate pooled mean results, and improvements in outcomes. RESULTS: Initial electronic and hand search identified 486 studies. After title and abstract review there were 38 that went on to full-text review. Finally, 22 studies were included in the final review. We identified 9 different non-operative treatment modalities; Corticosteroid injection, Alcohol injection, Extra-corporeal Shockwave therapy (ESWT), Radiofrequency Ablation (RFA), Cryoablation, Capsaicin injection, Botulinum toxin, Orthosis and YAG Laser Therapy. Corticosteroid showed a statistically significant reduction in mean VAS over all their studies (p < 0.01), with 50% success at 12 months. Alcohol showed promising short-term pain-relieving results only. Orthotics, Capsaicin injections, Cryoablation, Botulinum toxin, RFA and ESWT did show statistically significant improvements, but with limitation to their application. CONCLUSION: Following review, the authors would recommend the use of corticosteroid injections to treat Morton's neuromas. The authors feel that radio-frequency ablation and cryoablation would benefit from further well designed randomised controlled trials.


Assuntos
Tratamento Conservador/métodos , Neuroma Intermetatársico/terapia , Síndromes de Compressão Nervosa/terapia , Medidas de Resultados Relatados pelo Paciente , Humanos , Neuroma Intermetatársico/complicações , Síndromes de Compressão Nervosa/etiologia
10.
Postgrad Med J ; 93(1096): 91-95, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27729461

RESUMO

Trauma is one of the leading causes of death worldwide, with road traffic accidents being the leading cause of death in the age group of 15-29 years However, with modern advances in management and the introduction of specialised trauma centres, more and more are surviving severe and life-threatening trauma. The ideal timing of fracture fixation has been the subject of debate for a number of decades. There is evidence to suggest that fracture fixation in the patient with polytrauma is best achieved early on to reduce the incidence of morbidity and mortality, with damage control surgery in the more appropriate option in those patients who are haemodynamically unstable. However, early fracture fixation is not always possible, and the focus of this article is to review the common contributing factors resulting in delayed fixation. For the purpose of this discussion, we will consider all trauma as a single entity, taking into account that each type of fixation has its own complications, which are outside the scope of this article.


Assuntos
Medicina de Emergência/métodos , Fixação de Fratura/métodos , Unidades de Terapia Intensiva , Traumatismo Múltiplo/cirurgia , Centros de Traumatologia , Medicina de Emergência/educação , Fixação de Fratura/educação , Humanos , Escala de Gravidade do Ferimento , Guias de Prática Clínica como Assunto , Fatores de Tempo
11.
J Psychiatry Neurosci ; 41(4): E58-66, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27269205

RESUMO

BACKGROUND: Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance). METHODS: We recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate. RESULTS: A total of 121 patients participated in this study. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups. There were no significant differences in reduction of depression scores among the 3 groups. LIMITATIONS: The number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials, and the sham condition did not involve active stimulation. CONCLUSION: Our findings suggest that sequential bilateral rTMS is superior to sham rTMS; however, adjusting for coil-to-cortex distance did not yield enhanced efficacy rates.


Assuntos
Transtorno Depressivo Resistente a Tratamento/terapia , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Humanos , Imagem por Ressonância Magnética Intervencionista/métodos , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Estimulação Magnética Transcraniana/efeitos adversos , Resultado do Tratamento , Adulto Jovem
12.
J Psychosom Res ; 86: 7-12, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27302540

RESUMO

OBJECTIVE: Despite a lack of evidence, there is an assumption that patients with more complex psychiatric histories (CPH) prior to bariatric surgery have poor post-surgical weight loss and worsening psychiatric symptoms following surgery. Consequently, those with CPH are excluded from bariatric surgery in many bariatric clinics. This study examines whether psychiatric illness affects post-surgical weight loss and HRQOL, focusing on patients with CPH. METHOD: This prospective cohort study investigated 341 patients from a tertiary care centre bariatric surgery program who had surgery between September 2010 and October 2013. Patients were divided into CPH, other psychiatric disorder (OPD), or no psychiatric disorder (NPD) groups based on lifetime psychiatric diagnoses. Groups were compared one year post-surgery in regards to percent total weight loss (%TWL), mental and physical health related quality of life (HRQOL) using a Kruskal-Wallist test. Linear regression analysis was used to determine if mental illness group, gender, age, pre-op BMI, education, employment and relationship status predict change in %TWL and HRQOL. RESULTS: There was no significant difference in %TWL or physical HRQOL across groups. The CPH group experienced a decrease in mental HRQOL (p=0.0003). Mental illness severity predicted mental HRQOL (p=0.002) but not physical HRQOL or %TWL. CONCLUSION: Those with controlled CPH can achieve comparable weight loss compared to those with OPD or NPD. However, CPH may predict post-surgical decline in mental HRQOL. These findings demonstrate a need to reevaluate exclusion criteria to ensure equitable access to care, while continuing to monitor for psychiatric illness following surgery.


Assuntos
Cirurgia Bariátrica/psicologia , Transtornos Mentais/psicologia , Obesidade Mórbida/psicologia , Obesidade Mórbida/cirurgia , Qualidade de Vida/psicologia , Redução de Peso , Adulto , Cirurgia Bariátrica/tendências , Estudos de Coortes , Emprego , Feminino , Humanos , Masculino , Transtornos Mentais/cirurgia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo
13.
Breathe (Sheff) ; 11(2): 141-5, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26306114

RESUMO

A 67-year-old Caucasian male presented in January, 2013, with difficulty in breathing and pyrexia. This was following a course of antibiotics for a previous chest infection that had begun at the beginning of January and had not responded to therapy. His past medical history included chronic myeloid leukaemia, basal cell carcinoma of the throat treated in 2011, glaucoma and bilateral inguinal hernia repair (performed in 1989 and 2008). He was an ex-smoker of 21 years. His current medication was dasatinib (tyrosine kinase inhibitor) 100 µg⋅day(-1), amoxicillin/clavulanic acid 625 mg three-times daily orally (changed to 1.2 g three-times daily intravenously) and bimatoprost 0.1 mg eye drops.

15.
Dev Med Child Neurol ; 56(5): 421-33, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24237329

RESUMO

AIMS: The aims of this study were to (1) search the literature in order to identify the challenges facing adolescents and emerging adults with epilepsy; and (2) categorize these issues within both the framework of the International Classification of Functioning, Disability and Health (ICF) and an empirical model of quality of life (QOL) in childhood epilepsy. METHOD: We systematically searched PsycINFO, Ovid MEDLINE and Web of Science for studies reporting on QOL and health identified in people with epilepsy aged 12 to 29 years. Studies were limited to those that were published in the last 20 years in English, presenting the patient perspective. Data were extracted and charted using a descriptive analytical method. Identified issues were classified according to the ICF and QOL frameworks. RESULTS: Fifty four studies were identified. Another 62 studies with potentially useful information were included as an addendum. The studies highlight a range of psychosocial issues emphasizing peer acceptance, social isolation, and feelings of anxiety, fear, and sadness. INTERPRETATION: The ICF and QOL constructs represent useful starting points in the analytical classification of the potential challenges faced by adolescents with epilepsy. Progress is needed on fully classifying issues not included under these frameworks. We propose to expand these frameworks to include comorbidities, impending medical interventions, and concerns for future education, employment, marriage, dignity, and autonomy.


Assuntos
Epilepsia/psicologia , Qualidade de Vida , Transição para Assistência do Adulto , Adolescente , Adulto , Bases de Dados Factuais/estatística & dados numéricos , Pessoas com Deficiência/psicologia , Humanos
16.
Exp Eye Res ; 75(5): 529-42, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12457865

RESUMO

The purpose of these studies was to evaluate the effects of light damage on Japanese quail whose retinal carotenoids had been experimentally manipulated through altered diets. The birds were raised 6 months on a commercial turkey diet (T), on a custom carotenoid-deficient diet (C-) containing 90% less carotenoid than the T diet, or on Z+ diet [the C- diet supplemented with natural zeaxanthin (35mgkg(-1) food)]. Equal numbers of males and females on each diet were exposed to nine intervals (1hr on, 2hr off) of 3200lux cool white light, then placed in the dark for 14hr before tissue collection. One retina was immediately frozen for HPLC analysis; the other eye was immediately fixed and processed for microscopy. There were no significant differences in the retinal carotenoid concentrations in hatch-mates that were and were not exposed to light. Supplementation resulted in three- to four-fold increases in retinal zeaxanthin and no change in retinal lutein or alpha-tocopherol, but the C- diet did not reduce the retinal carotenoid concentration in C- birds below that in T birds. The light-exposed retinas had significant numbers of apoptotic photoreceptors and photoreceptor ghosts. The number of ghosts was negatively correlated with the number of dying photoreceptors (P<0.05), and with retinal concentrations of zeaxanthin, alpha-tocopherol or gamma-tocopherol (P<0.04, 0.02, 0.04, respectively), but not with lutein. The number of dying photoreceptors was positively correlated with alpha-tocopherol and the sum alpha-tocopherol plus zeaxanthin (P<0.1; P0.04). Photoreceptor death was semi-quantitatively scored, assuming that ghosts were formed by removal of apoptotic photoreceptors with nuclear condensation. Stepwise regression produced a good model (r(2)=0.67;P <0.0001) for predicting death scores from retinal concentrations of zeaxanthin (Standard Coefficient=-0.76) and lutein (Standard Coefficients=+0.43). Absence of lutein in gender-specific analyses suggests lutein served as surrogate marker for gender. Combined analysis of the C- and T birds also demonstrated that dying photoreceptors were negatively correlated with retinal zeaxanthin. These data confirm our previous report that retinal carotenoids prevent photoreceptor cell death, and provide the first direct evidence that retinal zeaxanthin protects photoreceptors from light-induced death.


Assuntos
Coturnix/fisiologia , Suplementos Nutricionais , Luz , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Doenças Retinianas/dietoterapia , beta Caroteno/análogos & derivados , beta Caroteno/farmacologia , Fatores Etários , Animais , Apoptose/efeitos dos fármacos , Carotenoides/análise , Feminino , Luteína/análise , Macula Lutea/patologia , Masculino , Doenças Retinianas/patologia , Fatores de Tempo , Tocoferóis/análise , Xantofilas , Zeaxantinas , beta Caroteno/administração & dosagem , beta Caroteno/análise
17.
Invest Ophthalmol Vis Sci ; 43(11): 3538-49, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12407166

RESUMO

PURPOSE: Inferential evidence indicates that macular pigments (lutein and zeaxanthin) protect photoreceptors and/or retard age-related macular degeneration. These experiments tested the hypothesis that retinal zeaxanthin prevents light-induced photoreceptor cell death. METHODS: Retinal damage was assessed in quail fed a carotenoid-deficient (C-) diet for 6 months. Groups of 16 birds (8 male, 8 female) were fed a C- diet supplemented with 35 mg 3R,3'R-zeaxanthin for 1, 3, or 7 days; one group was continued on C- diets. Half of each group was exposed to intermittent 3200-lux white light (10 1-hour intervals separated by 2 hours in dark). After 14 additional hours in the dark, one retina of each quail was collected for HPLC analysis, and the contralateral retina was embedded in paraffin for counts of apoptotic nuclei. RESULTS: After 7 days' supplementation, concentrations of zeaxanthin in serum, liver, and fat had increased by factors of 50.8, 43.2, and 6.5, respectively (all P < 0.001). In contrast, retinal zeaxanthin fluctuated significantly upward on day 3, but there was no net change on day 7. The number of apoptotic rods and cones in light-damaged eyes correlated significantly and inversely with zeaxanthin concentration in the contralateral retina (r = -0.61; P < 0.0001 and r = -0.54; P < 0.002), but not with serum zeaxanthin. Similar correlations were observed with retinal lutein, which correlated strongly with retinal zeaxanthin (r = 0.95; P < 0.0001). CONCLUSIONS: Retinal zeaxanthin dose dependently reduced light-induced photoreceptor apoptosis; elevated serum levels did not. These data provide the first experimental evidence that xanthophyll carotenoids protect photoreceptors in vivo.


Assuntos
Apoptose/efeitos da radiação , Células Fotorreceptoras de Vertebrados/efeitos da radiação , Lesões Experimentais por Radiação/prevenção & controle , Degeneração Retiniana/prevenção & controle , beta Caroteno/análogos & derivados , beta Caroteno/administração & dosagem , Tecido Adiposo/metabolismo , Animais , Contagem de Células , Cromatografia Líquida de Alta Pressão , Coturnix , Citoproteção , Dieta , Feminino , Luz , Fígado/metabolismo , Luteína/administração & dosagem , Masculino , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/patologia , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Retina/metabolismo , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Xantofilas , Zeaxantinas
18.
Invest Ophthalmol Vis Sci ; 43(4): 1210-21, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11923268

RESUMO

PURPOSE: The xanthophyll carotenoids (lutein and zeaxanthin) are hypothesized to delay progression of age-related macular degeneration. The quail has a cone-dominant retina that accumulates carotenoids. The purpose of these experiments was to characterize the carotenoid composition of retina, serum, liver, and fat in quail and to determine whether dietary enrichment with zeaxanthin alters zeaxanthin or lutein concentrations in these tissues. METHODS: Quail were fed for 6 months with a commercial turkey diet (T group; n = 8), carotenoid-deficient diet (C- group; n = 8), or a carotenoid-deficient diet supplemented with 35 mg 3R,3'R-zeaxanthin per kilogram of food, (Z+ group; n = 8). Zeaxanthin was derived from Sphingobacterium multivorum (basonym Flavobacterium). Carotenoids in serum, retina, liver, and fat were analyzed by HPLC. RESULTS: As in the primate fovea, the retina accumulated zeaxanthin, lutein, and cryptoxanthin, and preferentially absorbed zeaxanthin (P < 0.005). In contrast, lutein was preferentially absorbed by liver (P < 0.01) and fat (P < 0.0001). In supplemented females, zeaxanthin increased approximately 4-fold in retina, and 74-, 63- and 22-fold in serum, liver, and fat, respectively. In males, zeaxanthin was elevated approximately 3-fold in retina, and 42-, 17-, and 12-fold in serum, liver, and fat, respectively. Birds fed the Z+ diet absorbed a higher fraction of dietary lutein into serum, but lutein was reduced in the retina (P < 0.05). CONCLUSIONS: Xanthophyll profiles in quail mimic those in primates. Dietary supplements of zeaxanthin effectively increased zeaxanthin concentrations in serum, retina, liver, and fat. The robust response to zeaxanthin supplementation identifies the quail as an animal model for exploration of factors regulating delivery of dietary carotenoids to the retina.


Assuntos
Coturnix/metabolismo , Dieta , Luteína/metabolismo , beta Caroteno/administração & dosagem , beta Caroteno/metabolismo , Tecido Adiposo/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais , Absorção Intestinal , Fígado/metabolismo , Retina/metabolismo , Distribuição Tecidual , Xantofilas , Zeaxantinas , beta Caroteno/análogos & derivados
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