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1.
Ophthalmol Ther ; 13(7): 1925-1935, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38771461

RESUMO

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that causes severe and irreversible vision loss. The disease can therefore have a significant impact on the life of patients' and their families. The aim of this study was to evaluate the socio-economic burden of nAMD in Spain. METHODS: The annual cost per patient with nAMD was estimated for the first, second, and third year (or beyond) of treatment since diagnosis. Several cost categories were considered including direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labor productivity losses (LPL), and intangible costs (IC) related to loss of quality of life. The average annual cost per patient was estimated by assigning a unit price or financial proxy to the resources consumed per patient. Reference year of costs was 2021. RESULTS: The mean annual cost of nAMD was estimated at €17,265, €15,403, and €14,465 per patient in the first, second, and third year of treatment after diagnosis. There was an additional one-off cost of €744 associated with the diagnosis of nAMD. DHC accounted for most of the total annual cost per patient independent of the year of treatment since diagnosis (48% in year 1; 42% in year 2; 39% in year 3). Similarly, DNHC had an important contribution to the total costs (32% in year 1; 35% in year 2; 37% in year 3), followed by IC (20% in year 1; 23% in year 2; 24% in year 3), while the contribution of patients' LPL was minimal. CONCLUSION: This study estimated a high economic burden associated with nAMD for patients and their families, the healthcare system, and society at large. There is a need to improve the management of these patients to reduce the impact of nAMD disease progression.

2.
Ophthalmol Ther ; 13(7): 1937-1953, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38771462

RESUMO

INTRODUCTION: Diabetic macular oedema (DMO) is a complication of diabetic retinopathy that can result in vision loss. The disease can impact different spheres of a patient's life, including physical and psychological health, work, and activities of daily living, entailing an important use of healthcare and non-healthcare resources. This study aimed to estimate the socio-economic burden of DMO in Spain. METHODS: The burden of DMO was estimated from a societal perspective, per patient, year of treatment since diagnosis, and type of treatment. Four categories were considered: direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labour productivity losses (LPL), and intangible costs (IC) associated with loss of quality of life. Average annual costs were calculated by multiplying the resources used per patient by their corresponding unit price (or financial proxy). For a more accurate estimation, differences in resource use between treatments (intravitreal anti-vascular endothelial growth factor injections of ranibizumab or aflibercept, and intravitreal dexamethasone implants) and year since diagnosis (first, second, and third year or beyond) were considered and presented separately. The reference year for costs was 2021. RESULTS: The average annual costs of DMO in the first year of treatment after diagnosis was estimated at €18,774, €17,512, and €16,188 per patient treated with ranibizumab, aflibercept, and dexamethasone, respectively. This burden would be reduced to €15,783, €15,701, and €12,233 in the second year, and to €15,119, €15,043, and €12,790 in the third year, respectively. Diagnosis of DMO entails an additional one-off cost of €485. DHC accounted for the greatest proportion of total annual costs per patient, independent of the year, with LPL also making an important contribution to total costs. CONCLUSIONS: The socio-economic impact of DMO on patients, the healthcare system, and society at large is substantial. The constant increase in its prevalence accentuates the need for planning and implementation of healthcare strategies to prevent vision loss and reduce the socio-economic burden of the disease.

3.
Pharmaceuticals (Basel) ; 17(2)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38399372

RESUMO

Our objective was to evaluate changes in patient-reported outcome measures using the NEI-VFQ 25 questionnaire during a treat and extend regimen in naive neovascular Age-Related Macular Degeneration patients, and its correlation with anatomical and functional data. We conducted a prospective observational study. Patients underwent a treat and extend regimen with intravitreal ranibizumab for neovascular Age-Related Macular Degeneration. Initial response was evaluated at 4th month, and subsequently in every follow-up visit. If a clinical response was achieved, the injection interval was extended in two-week increments, up to a maximum of 12 weeks. Quality of life was assessed using the NEI-VFQ 25 questionnaire at baseline, 4th months, and 12th months. Patients were categorized as good or poor responders based on Best corrected visual acuity, central foveal thickness, intraretinal fluid, or subretinal fluid. Treatment with ranibizumab led to a significant improvement in quality of life, with a mean increase in NEI-VFQ 25 score of 4.27 points in the 12th month. No significant differences in improvement were observed between good and poor responders. Quality of life scores in neovascular Age-Related Macular Degeneration patients improved with intravitreal treatment regardless of the clinical response. The early response following the loading phase could indicate better quality of life after one year of treatment, with Best corrected visual acuity being the clinical parameter with the greatest influence on quality of life.

4.
Pharmaceutics ; 16(1)2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38258115

RESUMO

Anti-vascular endothelial growth factor drugs keep being the main therapy for neovascular age-related macular degeneration (AMD). Possible predictive parameters (demographic, biochemical and/or inflammatory) could anticipate short-term treatment response with ranibizumab. 46 treatment-naive patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD and the clinical examination was made at baseline and one month after the third injection. Demographic characteristics, co-morbidities and concomitant treatments were recorded at the baseline visit. Biochemical parameters, complete blood count and inflammation biomarkers were also measured at these times. Uric Acid was found to be statistically significant with a one-point difference between good and poor responders in both basal and treated patients, but only in basal parameters was statistical significance reached (p = 0.007 vs. p = 0.071 in treated patients). Cholesterol and inflammatory parameters such as white blood cell count and neutrophils were significantly reduced over time when treated with intravitreal ranibizumab. On the other hand, women seemed to have a worse prognosis for short-term response to intravitreal ranibizumab treatment. Uric acid may help identify possible non-responders before initial treatment with ranibizumab, and cholesterol and white blood cells could be good candidates to monitor short-term response to ranibizumab treatment.

5.
Invest Ophthalmol Vis Sci ; 64(13): 34, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37862026

RESUMO

Purpose: To determine whether genetic risk single nucleotide polymorphisms (SNPs) for age-related macular degeneration (AMD) influence short-term response to intravitreal ranibizumab treatment. Methods: Forty-four treatment-naive AMD patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD. After an initial clinical examination (baseline measurement), a follow-up visit was performed to determine treatment response one month after the third injection (treatment evaluation). Patients were evaluated based on ophthalmoscopy, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography. Peripheral venous blood was collected for DNA analysis at baseline visit. Patients were genotyped for single-nucleotide polymorphisms within AMD-relevant genes and classified on good or poor responders based on visual acuity, central retinal thickness, intraretinal fluid, and subretinal fluid. Results: One hundred ten AMD-associated SNPs have been analyzed. Six were found to be relevant when associated to ranibizumab treatment response. The genetic variants rs890293 (CYP2J2), rs11200638 (HTRA1), rs405509 (APOE), rs9513070 (FLT1), and rs8135665 (SLC16A8) predisposed patients to a good response, whereas rs3093077 (CRP) was associated with a poor response. FTL1, SLC16A8, and APOE were the SNPs that showed significance (P < 0.05) but did not pass Bonferroni correction. Conclusions: This is the first study that links novel polymorphisms in genes such as CRP, SCL16A8, or CYP2J2 to treatment response to ranibizumab therapy. On the other hand, HTRA1, FLT1, and APOE are linked to a good ranibizumab response. These SNPs may be good candidates for short-term treatment response biomarkers in AMD patients. However, further studies will be necessary to confirm our findings.


Assuntos
Ranibizumab , Degeneração Macular Exsudativa , Humanos , Ranibizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Citocromo P-450 CYP2J2 , Fator A de Crescimento do Endotélio Vascular/genética , Acuidade Visual , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/genética , Polimorfismo de Nucleotídeo Único , Apolipoproteínas E , Injeções Intravítreas , Tomografia de Coerência Óptica , Resultado do Tratamento
6.
Retina ; 42(3): 465-475, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34914345

RESUMO

PURPOSE: To describe clinical and ophthalmologic features and outcomes of patients with coronavirus disease-19 with retinal vascular occlusions. METHODS: Retrospective multicenter case series and PubMed review of cases reported from March 2020 to September 2021. Outcome measures are as follows: type of occlusion, treatments, best-corrected visual acuity, and central macular thickness on optical coherence tomography. RESULTS: Thirty-nine patients were identified. Fifteen patients with a median age of 39 (30-67) years were included in the multicenter study. Vascular occlusions included central retinal vein occlusion (12 eyes), branch retinal vein occlusion (4 eyes), and central retinal artery occlusion (2 eyes). Three cases were bilateral. Baseline best-corrected visual acuity was 20/45 (no light perception-20/20). Baseline central macular thickness was 348.64 (±83) µm. Nine eyes received anti-vascular endothelial growth factor agents, dexamethasone intravitreal implant, or both. Final best-corrected visual acuity was 20/25 (no light perception-20/20), and central macular thickness was 273.7 ± 68 µm (follow-up of 19.6 ± 6 weeks). Among the 24 cases from the literature review, retinal vein occlusion was the predominant lesion. Clinical characteristics and outcomes were similar to those found in our series. CONCLUSION: Coronavirus disease-19-associated retinal vascular occlusions tend to occur in individuals younger than 60 years. Retinal vein occlusion is the most frequent occlusive event, and outcomes are favorable in most cases.


Assuntos
COVID-19/diagnóstico , Infecções Oculares Virais/diagnóstico , Oclusão da Veia Retiniana/diagnóstico , SARS-CoV-2/isolamento & purificação , Adulto , Idoso , Inibidores da Angiogênese/uso terapêutico , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Dexametasona/uso terapêutico , Implantes de Medicamento , Infecções Oculares Virais/tratamento farmacológico , Infecções Oculares Virais/virologia , Feminino , Angiofluoresceinografia , Glucocorticoides/uso terapêutico , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Oclusão da Veia Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/virologia , Estudos Retrospectivos , SARS-CoV-2/genética , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Tratamento Farmacológico da COVID-19
7.
Int Ophthalmol ; 41(10): 3427-3436, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34110547

RESUMO

PURPOSE: To describe and evaluate the main direct health costs, in routine clinical practice, of age-related macular degeneration (AMD) patients, from hospital perspective, in Spain. METHODS: Retrospective, multicenter, and observational study conducted on five third-level Spanish hospitals, between December 2018 and December 2019. The study included patients who were diagnosed of AMD before December 2018. Direct healthcare costs were obtained from a Spanish database. Study variables included demographic and clinical variables, and resources, such as treatment, diagnostic tests, medical examination, and surgery. Among the 1414 screened AMD patients, 1164 patients were included. In the overall study patients, the total cost was €5,386,511.0, with a mean cost per patient of €4627.6 ± 2383.9. The largest cost items were diagnostic examinations (€2.832.902,0) and vascular endothelial growth factor inhibitors (anti-VEGF) treatment (€2.038.257,2). Bevacizumab was administered to 325 (27.9%) patients, ranibizumab to 328 (28.2%), and aflibercept to 626 (53.8%); 115 (10.7%) patients received two anti-VEGF treatments, while 90 (7.7%) did not receive any. Over the course of the study, a total of 6,057 anti-VEGF injections were administered, with a mean (95% confidence interval) of 4.8 (4.4-5.2) injections per patient. Regarding safety, 29 patients experience injection-related adverse events, among them 12 patients had cataract and 11 ones elevated intraocular pressure (IOP). The incidence of endophthalmitis was 0.5% (6/1164). CONCLUSIONS: AMD was associated with considerable healthcare costs for regional healthcare systems. Diagnostic examinations, particularly OCT examinations, and anti-VEGF treatment represented the largest cost items.


Assuntos
Degeneração Macular , Fator A de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Efeitos Psicossociais da Doença , Humanos , Injeções Intravítreas , Degeneração Macular/diagnóstico , Degeneração Macular/tratamento farmacológico , Degeneração Macular/epidemiologia , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Acuidade Visual
8.
Nutrients ; 13(4)2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33920232

RESUMO

The purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of -1.63 (95% CI -0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD.


Assuntos
Suplementos Nutricionais/efeitos adversos , Degeneração Macular/dietoterapia , Nutrientes/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/efeitos adversos , Feminino , Humanos , Luteína/administração & dosagem , Luteína/efeitos adversos , Degeneração Macular/sangue , Degeneração Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Nutrientes/efeitos adversos , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/efeitos adversos , Álcool Feniletílico/análogos & derivados , Resveratrol/administração & dosagem , Resveratrol/efeitos adversos , Resultado do Tratamento , Acuidade Visual , Xantofilas/administração & dosagem , Zeaxantinas/administração & dosagem , Zeaxantinas/efeitos adversos
9.
Curr Med Chem ; 27(4): 583-598, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31362645

RESUMO

Age-related macular degeneration is an acquired degenerative disease that is responsible for severe loss of vision in elderly people. There are two types: dry age-related macular degeneration and wet age-related macular degeneration. Its treatment has been improved and tries to be tailored in the future. The aim of this review is to summarize the pharmacological advances in the treatment of age-related macular degeneration. Regarding dry AMD, there is no effective treatment to reduce its progression. However, some molecules such as lampalizumab and eculizumab were under investigation, although they have shown low efficacy. Herein, in an attempt to prevent dry AMD progression, the most important studies suggested increasing the antioxidants intake and quitting the smoke habit. On the other hand, wet AMD has more developed treatment. Nowadays, the gold standard treatment is anti-VEGF injections. However, more effective molecules are currently under investigation. There are different molecules under research for dry AMD and wet AMD. This fact could help us treat our patients with more effective and lasting drugs but more clinical trials and safety studies are required in order to achieve an optimal treatment.


Assuntos
Degeneração Macular/tratamento farmacológico , Idoso , Inibidores da Angiogênese , Bevacizumab , Humanos , Degeneração Macular/dietoterapia , Ranibizumab , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular
10.
Curr Med Chem ; 27(4): 549-569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31296152

RESUMO

The current review is focussing different factors that contribute and directly correlate to the onset and progression of Age-related Macular Degeneration (AMD). In particular, the susceptibility to AMD due to genetic and non-genetic factors and the establishment of risk scores, based on the analysis of different genes to measure the risk of developing the disease. A correlation with the actual therapeutic landscape to treat AMD patients from the point of view of pharmacokinetics and pharmacogenetics is also exposed. Treatments commonly used, as well as different regimes of administration, will be especially important in trying to classify individuals as "responders" and "non-responders". Analysis of different genes correlated with drug response and also the emerging field of microRNAs (miRNAs) as possible biomarkers for early AMD detection and response will be also reviewed. This article aims to provide the reader a review of different publications correlated with AMD from the molecular and kinetic point of view as well as its commonly used treatments, major pitfalls and future directions that, to our knowledge, could be interesting to assess and follow in order to develop a personalized medicine model for AMD.


Assuntos
Degeneração Macular , Farmacogenética , Bevacizumab , Biomarcadores , Humanos , Medicina de Precisão
13.
Curr Diabetes Rev ; 5(1): 18-25, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19199894

RESUMO

Diabetic macular edema is an important cause of visual loss in the developed world and may frequently lead to irreversible changes in visual acuity. The Early Treatment Diabetic Retinopathy Study showed a significant benefit in using focal laser photocoagulation for the treatment of macular edema, more specifically defined as clinically significant macular edema. However, some cases of diabetic macular edema are refractory to laser therapy and do not have a good prognosis with such treatment. Triamcinolone acetonide is glucocoticosteroid with antiangiogenic and antiedematous properties. Recently, some promising results, respect to the increases of visual acuity and decreases in foveal thickness, have been shown in different studies for the treatment of refractory diabetic macular edema with intravitreal triamcinolone acetonide.


Assuntos
Anti-Inflamatórios/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Corpo Vítreo/fisiopatologia , Anti-Inflamatórios/administração & dosagem , Retinopatia Diabética/cirurgia , Fóvea Central/patologia , Humanos , Edema Macular/etiologia , Modelos Moleculares , Tomografia de Coerência Óptica , Triancinolona Acetonida/química , Vitrectomia , Corpo Vítreo/efeitos dos fármacos
14.
J Refract Surg ; 23(3): 299-304, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17385297

RESUMO

PURPOSE: To investigate the cell populations and structural alterations of the cornea in an experimental model of diffuse lamellar keratitis (DLK) using confocal microscopy and histopathology. METHODS: A corneal flap was cut in 22 eyes of 11 New Zealand rabbits and the stromal interface was exposed to balanced salt solution (BSS, BSS group) and Pseudomonas aeruginosa lipopolysaccharide (LPS) endotoxin (5 mg/mL) (LPS 5 mg/mL group) and (3.5 mg/mL) (LPS 3.5 mg/mL group). Postoperatively, eyes were examined with a slit-lamp microscope (DLK grading) and confocal microscopy. Animals were sacrificed on day 3 (BSS group and LPS 5 mg/mL group) and day 4 (LPS 3.5 mg/mL group). Corneoscleral buttons were excised and processed for histopathologic examination. RESULTS: Seven eyes were excluded. Slit-lamp microscopy revealed no cellular infiltration in the BSS group (five eyes). In the LPS groups, all eyes developed DLK, with iritis only observed in grade III eyes. In the LPS 5 mg/mL group, four eyes had DLK grade III, with iritis in three eyes. In the LPS 3.5 mg/mL group, three eyes had grade II and three eyes had grade III with iritis. On confocal microscopy, the BSS group had no cellular infiltration. Dense accumulation of inflammatory cells at the interface was noted in both LPS groups. Histopathology in the BSS group had a normal appearance. In the LPS groups, an inflammatory infiltrate was present at the interface that consisted of three cell populations--eosinophils, neutrophils, and lymphocytes. CONCLUSIONS: Lipopolysaccharide endotoxin induced DLK in all exposed eyes, with iritis in a considerable proportion of eyes. The infiltrate consisted of three cell populations. Confocal microscopy showed the infiltrate in all affected eyes. Histopathological and confocal microscopic findings correlated well with the clinical appearance.


Assuntos
Substância Própria/patologia , Infecções Oculares Bacterianas/patologia , Ceratite/patologia , Microscopia Confocal , Infecções por Pseudomonas/patologia , Retalhos Cirúrgicos/patologia , Animais , Substância Própria/microbiologia , Modelos Animais de Doenças , Infecções Oculares Bacterianas/microbiologia , Ceratite/microbiologia , Infecções por Pseudomonas/microbiologia , Coelhos , Retalhos Cirúrgicos/microbiologia
15.
Optom Vis Sci ; 83(8): 546-9, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16909080

RESUMO

PURPOSE: The purpose of this study is to describe a patient with retinal angiomatous proliferation (RAP) treated successfully by photodynamic therapy. METHODS: A 74-year-old white woman was referred to our clinic for evaluation as a result of progressive decrease of vision in the right eye. Visual acuity was 20/100 in the affected right eye. The findings of fluorescein and indocyanine green angiography were consistent with a diagnosis of RAP, and cystoid macular edema was also revealed by optical coherence tomography (OCT). Photodynamic therapy (PDT) was carried out because of visual deterioration and localization of the RAP. RESULTS: The RAP was treated with PDT, and an improvement in visual acuity to 20/60 was noted 4 months after treatment and 20/40 after 6 months. The resolution of the lesion was confirmed by fluorescein angiography, indocyanine green angiography, and OCT. CONCLUSIONS: Photodynamic therapy can be effective for the treatment of RAP when it is associated with visual acuity decrease and is located near the fovea.


Assuntos
Degeneração Macular/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Retina/patologia , Idoso , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Degeneração Macular/patologia , Tomografia de Coerência Óptica , Acuidade Visual
16.
Neurosci Res ; 55(3): 292-9, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16650497

RESUMO

Catecholaminergic and angiotensinergic systems are involved in the neural control of blood pressure. The present study analysed the expression of tyrosine hydroxylase (TH), a key enzyme for catecholamine synthesis and of angiotensinogen (AGT), the precursor of angiotensin II (Ang II), in areas of the central nervous system (CNS) involved with cardiovascular regulation such as nucleus tractus solitarius (NTS), ventrolateral medulla (VLM), locus coeruleus (LC) and hypothalamic paraventricular nucleus (PVN) 2 h, 3 and 7 days after aortic coarctated hypertensive rats. In situ hybridization, was employed for the analysis of messenger RNA (mRNA) expression with anatomical resolution. No changes were seen in TH and AGT mRNA expression in the analysed areas 2 h and 3 days after aortic coarctation when compared to the respective sham group. TH mRNA expression was increased in the NTS and LC of rats 7 days after coarctation hypertension when compared to sham rats. Time course analysis, showed an increase in TH mRNA expression in the NTS 7 days after aortic coarctation when compared to 2 h and 3 days groups, as well as an increase in LC 3 days and 7 days following coarctation hypertension in comparison with the 2 h group. Analysis of AGT mRNA in the NTS expression revealed a decrease at 3 days, followed by an increase in mRNA expression 7 days following coarctation hypertension when compared to the sham group. Time course analysis, showed an increase in AGT mRNA expression in the NTS 7 days after coarctation when compared to 2 h and 3 days groups. The results show that TH and AGT mRNA expression changes during the different phases of experimental hypertension, suggesting that the noradrenaline (NOR) and angiotensin II (Ang II) might participate in the modulation/maintenance of coarctation hypertension.


Assuntos
Angiotensinogênio/genética , Encéfalo/metabolismo , Hipertensão/genética , Hipertensão/metabolismo , RNA Mensageiro/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Angiotensina II/biossíntese , Animais , Coartação Aórtica/complicações , Coartação Aórtica/fisiopatologia , Pressão Sanguínea/genética , Encéfalo/fisiopatologia , Tronco Encefálico/metabolismo , Catecolaminas/biossíntese , Modelos Animais de Doenças , Expressão Gênica/fisiologia , Hipertensão/fisiopatologia , Masculino , Núcleo Hipotalâmico Paraventricular/metabolismo , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos WKY , Fatores de Tempo , Regulação para Cima/genética
17.
Brain Res Bull ; 64(1): 59-66, 2004 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-15275958

RESUMO

Calcitonin gene-related peptide (alpha CGRP) and galanin (GAL) are peptides known to participate in central mechanisms of blood pressure control. Nonetheless, variations in the synthesis of the peptides in response to a hypertensive challenge are not well described, specially using a model, which allows acute and chronic analyses. In this study, we have employed in situ hybridization to analyse changes in mRNA expression of alpha CGRP and GAL in the nucleus tractus solitarii (NTS), hypothalamic paraventricular nucleus (PVN) as well as petrosal and nodose ganglia after aortic coarctation-induced hypertension in rats. Acute (2h) and chronic (3 and 7 days) analyses were performed in order to evaluate the involvement of both peptides in different periods of hypertension. The analysis of relative mRNA levels showed significant differences between sham-operated and aortic coarcted hypertensive rats. alpha CGRP mRNA expression was decreased 2h (40%) and 3 days (42%) in nodose and petrosal ganglia, respectively, after coarctation. No changes in CGRP mRNA signal were seen in the NTS and PVN in the analysed periods. GAL mRNA expression was decreased in the NTS (19%) and PVN (55%), 3 and 7 days, respectively, after coarctation-induced hypertension. No changes in GAL mRNA expression were observed in petrosal and nodose ganglia following aortic coarctation. Data suggest that alpha CGRP and GAL may participate in the mechanisms involved in the establishment/maintenance of hypertension induced by aortic coarctation. Acute changes might be involved with the adaptation to the hypertensive state, while changes at the chronic phase might be related to counteraction of hypertension.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Galanina/metabolismo , Hipertensão/metabolismo , Neurônios/metabolismo , Nervos Periféricos/citologia , Animais , Pressão Sanguínea/fisiologia , Peptídeo Relacionado com Gene de Calcitonina/genética , Galanina/genética , Hipertensão/fisiopatologia , Hibridização In Situ/métodos , Masculino , Gânglio Nodoso/metabolismo , Núcleo Hipotalâmico Paraventricular/citologia , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos WKY , Núcleo Solitário/citologia , Fatores de Tempo
18.
Neuropeptides ; 38(2-3): 77-82, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15223269

RESUMO

Neuropeptide Y (NPY) is known to participate in central mechanisms of blood pressure control. However, variations on the expression of its receptors in response to a hypertensive challenge are not well defined, specially when considering that Y1 and Y2 often mediate opposite responses. In this study we have employed in situ hybridization to analyze changes in mRNA expression of NPY receptor subtypes Y1 and Y2 in the nucleus tractus solitarii (NTS), paraventricular nucleus of the hypothalamus (PVN) and petrosal and nodose ganglions 2 h, 3 and 7 days after aortic coarctation induced hypertension. Quantification by image analysis showed significant differences between sham-operated and aortic-coarcted hypertensive rats. Y1 receptor mRNA expression was increased (39%) in petrosal ganglion, 3 days after surgery. Y2 receptor mRNA expression was increased (143%) in the NTS of hypertensive compared with sham rats 2 h after surgery. Y2 receptor mRNA was decreased (62%) in the nodose ganglion of hypertensive compared with sham rats 2 h after surgery. No change was seen in Y1 and Y2 mRNA expression in the PVN in any analyzed period. The data suggest that NPY Y1 and Y2 receptors might participate in the mechanisms involved in the establishment/maintenance of hypertension induced by aortic coarctation. Acute changes seem to be involved with the adaptation to the new hypertensive state.


Assuntos
Encéfalo/metabolismo , Nervos Periféricos/metabolismo , Receptores de Neuropeptídeo Y/biossíntese , Animais , Nervo Glossofaríngeo/metabolismo , Hibridização In Situ , Masculino , Gânglio Nodoso/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , RNA Mensageiro/biossíntese , Ratos , Ratos Endogâmicos WKY , Receptores de Neuropeptídeo Y/genética , Núcleo Solitário/metabolismo
19.
Nephrologie ; 15(2): 113-5, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8047194

RESUMO

UNLABELLED: A prospective study was done during a six-month period to evaluate number, function, difficulties of placement and immediate and late complications of central venous catheters for hemodialysis. One hundred and three catheters were placed, 78 double lumen and 25 single lumen, using Seldinger technique. The places of implantation were: right subclavian in 79, left subclavian in 13, right jugular in 8 and 3 in the right femoral vein; 62 were first catheters. We needed a mean of 2 punctures to enter the goal vein, and in 4 the place of implantation had to be changed. Catheters remained in place for a mean of 21 days. Six catheters were lost to follow-up. Immediate complications were 2 hemothorax, 3 punctures of the artery and 3 malpositioned catheters. Late complications were 12 local infections, 7 associated with sepsis. Twenty catheters occluded but removal was only necessary in 10. There was no statistic difference in incidence of complications between single lumen and double lumen catheters (X2). CONCLUSIONS: 1. Percutaneous central venous catheters is a simple and safe technique to obtain temporary vascular access for hemodialysis. 2. Double lumen catheters have no higher rate of complications than single lumen.


Assuntos
Cateterismo Venoso Central , Cateteres de Demora , Diálise Renal , Lesões das Artérias Carótidas , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/estatística & dados numéricos , Cateteres de Demora/efeitos adversos , Cateteres de Demora/estatística & dados numéricos , Veia Femoral , Hemotórax/etiologia , Humanos , Infecções/etiologia , Veias Jugulares , Estudos Prospectivos , Punções , Veia Subclávia
20.
Rev Port Cardiol ; 10(6): 497-501, 1991 Jun.
Artigo em Português | MEDLINE | ID: mdl-1931109

RESUMO

OBJECTIVE: To characterize and to quantitate the morphologic changes in left ventricle, in renal transplant patients (Pts) treated with cyclosporine, through sequential echocardiographic examinations. DESIGN: A prospective study of renal transplant patients, between October/88 and May/89, who maintained good function of the renal graft during the follow-up. SETTING: Cardiology and Nephrology departments of Santo António Hospital. MATERIAL AND METHODS: 20 patients, 13 men and 7 women, mean age of 33 +/- 10, ranging from 20 to 56, constitute the final group of the study. These patients have been receiving dialysis during 3.8 +/- 2.3 years (0.4-8). Seven patients were excluded, five by echocardiographic criteria and another two because of chronic renal graft disfunction (creatinine greater than 2.0 mg%). The echocardiographic examinations were performed during the first week, and 1, 2, 3, 6 and 12 months after renal transplantation. The following measurements were performed: left ventricular end-diastole diameter (LVED), interventricular septal thickness (IVST), posterior wall thickness (PWT) and left ventricular mass index (LVMI). The measurements were obtained in M-mode following the conventional recommendations. Average values of at least 3 cardiac cycles were used. Heart rate, blood pressure, creatinine, hematocrit, body surface area and fistula patency, were determined at the time of each echocardiogram. MAIN RESULTS: The LVED decreased progressively until the third month, from 51.9 +/- 7 mm to 47.8 +/- 6 mm (p less than 0.001), remaining stable thereafter. The baseline value of IVST, 13.6 +/- 5 mm, was similar at the twelfth month, 13.8 +/- 2 mm (ns). The baseline value of PWT, 13.7 +/- 4 mm, decreased gradually since the second month, having reached 12.7 +/- 2 mm at the twelfth month (ns). The LVMI (g/m2) reduced progressively, from 243 +/- 82 to 190 +/- 38 at the end of the study (p less than 0.05. A high incidence of arterial hypertension was detected during the follow-up period; at the twelfth month, 18 patients (90%) were on antihypertensive drug therapy, 11 of which had blood pressure greater than or equal to 160/95 mmHg. CONCLUSIONS: We verified, one year after the renal transplantation, a significant decrease of LVMI, that was mainly determined by the LVED reduction. Left ventricular walls thickness had no significant variation; we think that the high incidence of hypertension during the follow-up period, in part due to the pressure effect of cyclosporine, may have been responsible for this fact.


Assuntos
Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Transplante de Rim , Adulto , Feminino , Seguimentos , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade
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