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1.
J Oncol Pharm Pract ; 29(7): 1793-1796, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37455486

RESUMO

INTRODUCTION: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with drugs with different mechanisms of action, including anti-hypertensives, tumour necrosis factor-α inhibitors and even some chemotherapy medicines. In the last years, a few reports have been described in patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib. CASE REPORT: Here, we describe a case of DI-SCLE in association with ribociclib and exemestane in a woman diagnosed with metastatic breast cancer. MANAGEMENT AND OUTCOME: Topical mometasone was prescribed for two weeks with complete resolution of lesions, also abemaciclib was substituted for ribociclib, and the patient had stable disease with no relapse of DI-SCLE. DISCUSSION: To our knowledge, this is the first report of ribociclib-induced SCLE but based on the DI-SCLE reported cases associated others CDK4/6 inhibitors, the role of this family of drugs in dermatopathology must be further investigated.


Assuntos
Neoplasias da Mama , Lúpus Eritematoso Cutâneo , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia , Lúpus Eritematoso Cutâneo/induzido quimicamente , Lúpus Eritematoso Cutâneo/patologia
2.
Adv Ther ; 39(7): 3180-3198, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35553372

RESUMO

INTRODUCTION: Novel glucagon-like peptide-1 (GLP-1) receptor agonist oral semaglutide has demonstrated greater improvements in glycated hemoglobin (HbA1c) and body weight versus oral medications empagliflozin and sitagliptin, and injectable GLP-1 analog liraglutide, in the PIONEER clinical trial program. Based on these data, the present analysis aimed to evaluate the long-term cost-effectiveness of oral semaglutide versus empagliflozin, sitagliptin and liraglutide in Spain. METHODS: Outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 3.0% annually. Cohort characteristics and treatment effects were sourced from PIONEER 2 and 4 for the comparisons of oral semaglutide 14 mg versus empagliflozin 25 mg and liraglutide 1.8 mg, respectively, and PIONEER 3 for oral semaglutide 7 and 14 mg versus sitagliptin 100 mg. Costs were accounted from a healthcare payer perspective in 2020 euros (EUR). Patients were assumed to receive initial therapies until HbA1c exceeded 7.5% and then treatment-intensified to basal insulin. RESULTS: Oral semaglutide 14 mg was associated with improvements in quality-adjusted life expectancy of 0.13, 0.19 and 0.06 quality-adjusted life years (QALYs) versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg, respectively, with direct costs EUR 168 higher versus empagliflozin and EUR 236 and 1415 lower versus sitagliptin and liraglutide, respectively. Oral semaglutide 14 mg was associated with an incremental cost-effectiveness ratio (ICER) of EUR 1339 per QALY gained versus empagliflozin and was considered dominant (clinically superior and cost saving) versus sitagliptin and liraglutide. Additional analyses demonstrated that oral semaglutide 7 mg was associated with improvements of 0.11 QALYs and increased costs of EUR 226 versus sitagliptin and was therefore associated with an ICER of EUR 2011 per QALY gained. CONCLUSION: Oral semaglutide 14 mg was dominant versus sitagliptin and liraglutide, and cost-effective versus empagliflozin, for the treatment of type 2 diabetes in Spain.


Assuntos
Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Administração Oral , Compostos Benzidrílicos/uso terapêutico , Ensaios Clínicos como Assunto , Análise Custo-Benefício , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/economia , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Glucosídeos/uso terapêutico , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Fosfato de Sitagliptina/uso terapêutico , Espanha
3.
Adv Ther ; 37(10): 4427-4445, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32862365

RESUMO

INTRODUCTION: Healthcare systems aim to maximize the health of the population, but must work within constrained budgets. Therefore, choosing therapies that are both effective and cost-effective is paramount. The present analysis assessed the cost-effectiveness of once-weekly semaglutide 0.5 mg and 1 mg versus once-weekly dulaglutide 1.5 mg and versus once daily sitagliptin 100 mg for the treatment of patients with type 2 diabetes with inadequate glycemic control on oral anti-hyperglycemic medications over patient lifetimes from a healthcare payer perspective in the Spanish setting. METHODS: Cost and clinical outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Baseline cohort characteristics and treatment effects on initiation of semaglutide 0.5 mg and 1 mg, dulaglutide 1.5 mg and sitagliptin 100 mg were based on the once-weekly semaglutide clinical trial program (SUSTAIN 7 and 2). Captured costs included treatment costs and costs of diabetes-related complications. Projected outcomes were discounted at 3.0% annually. RESULTS: Projections of long-term clinical outcomes indicated that once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in discounted life expectancy of 0.02 and 0.11 years, respectively, and discounted quality-adjusted life expectancy of 0.03 and 0.11 quality-adjusted life years (QALYs), respectively, versus dulaglutide 1.5 mg. Compared with sitagliptin, once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in discounted life expectancy of 0.17 and 0.24 years, respectively and discounted quality-adjusted life expectancy of 0.16 and 0.23 QALYs. The increased duration and quality of life with once-weekly semaglutide 0.5 mg and 1 mg resulted from a reduced cumulative incidence and delayed time to onset of diabetes-related complications. Avoided complications resulted in once-weekly semaglutide 0.5 mg and 1 mg being cost-saving versus dulaglutide 1.5 mg and versus sitagliptin 100 mg from a healthcare payer perspective. CONCLUSIONS: Once-weekly semaglutide 0.5 mg and 1 mg were considered dominant (more effective and less costly) versus sitagliptin 100 mg and dulaglutide 1.5 mg for the treatment of patients with type 2 diabetes with inadequate glycemic control on oral anti-hyperglycemic medications and are likely to be a good use of healthcare resources in the Spanish setting.


Since healthcare systems aim to maximize the health of the population but must work within constrained budgets, choosing therapies that are both effective and cost-effective is paramount. We assessed the cost-effectiveness, from a Spanish healthcare payer perspective, of the newly marketed once-weekly semaglutide 0.5 mg and 1 mg versus two established therapies (dulaglutide 1.5 mg and sitagliptin 100 mg) for the treatment of patients with type 2 diabetes with inadequate glycemic control on oral anti-hyperglycemic medications over patient lifetimes.Outcomes were projected using a computer simulation model, based on two trials conducted as part of the once-weekly semaglutide clinical trial program (SUSTAIN 2 and SUSTAIN 7). Captured costs included treatment costs and costs of diabetes-related complications.Projections of long-term clinical outcomes indicated that once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in quality-adjusted life expectancy of 0.03 and 0.11 quality-adjusted life years (QALYs), respectively, versus dulaglutide 1.5 mg, and 0.16 and 0.23 QALYs, respectively, versus sitagliptin 100 mg. The increased duration and quality of life with once-weekly semaglutide 0.5 mg and 1 mg resulted from a reduced cumulative incidence and delayed time to onset of diabetes-related complications. Avoided complications resulted in once-weekly semaglutide 0.5 mg and 1 mg being cost-saving versus dulaglutide 1.5 mg and versus sitagliptin 100 mg.Once-weekly semaglutide 0.5 mg and 1 mg were more effective and less costly and therefore were considered dominant in both comparisons, and are likely to be a good use of healthcare resources in the Spanish setting.


Assuntos
Diabetes Mellitus Tipo 2 , Fosfato de Sitagliptina , Análise Custo-Benefício , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Humanos , Hipoglicemiantes , Fragmentos Fc das Imunoglobulinas , Qualidade de Vida , Proteínas Recombinantes de Fusão
4.
J Med Econ ; 23(2): 193-203, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31613199

RESUMO

Aims: Controlling costs while maximizing healthcare gains is the predominant challenge for healthcare providers, and therefore cost-effectiveness analysis is playing an ever-increasing role in healthcare decision making. The aim of the present analysis was to assess the long-term cost-effectiveness of subcutaneous once-weekly semaglutide (0.5 mg and 1 mg) versus empagliflozin (10 mg and 25 mg) in the Spanish setting for the treatment of patients with type 2 diabetes (T2D) with inadequate glycemic control on oral anti-hyperglycemic medications.Material and methods: The IQVIA CORE Diabetes Model was used to project outcomes over patient lifetimes with once-weekly semaglutide versus empagliflozin, with treatment effects based on a network meta-analysis. The analysis captured treatment costs, costs of diabetes-related complications, and the impact of complications on quality of life, based on published sources. Outcomes were discounted at 3.0% per annum.Results: Once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in discounted quality-adjusted life expectancy of 0.12 and 0.15 quality-adjusted life years (QALYs), respectively, versus empagliflozin 10 mg and improvements of 0.11 and 0.14 QALYs, respectively, versus empagliflozin 25 mg. Treatment costs were higher with once-weekly semaglutide compared with empagliflozin, but this was partially offset by cost savings due to avoidance of diabetes-related complications. Once-weekly semaglutide 0.5 mg and 1 mg were associated with incremental cost-effectiveness ratios of EUR 2,285 and EUR 161 per QALY gained, respectively, versus empagliflozin 10 mg, and EUR 3,090 and EUR 625 per QALY gained, respectively, versus empagliflozin 25 mg.Conclusions: Based on a willingness-to-pay threshold of EUR 30,000 per QALY gained, once-weekly semaglutide 0.5 mg and 1 mg were projected to be cost-effective versus empagliflozin 10 mg and 25 mg for the treatment of patients with T2D with inadequate glycemic control on oral anti-hyperglycemic medications in the Spanish setting, irrespective of patients' BMI at baseline.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/economia , Pressão Sanguínea , Peso Corporal , Análise Custo-Benefício , Complicações do Diabetes/economia , Complicações do Diabetes/prevenção & controle , Vias de Administração de Medicamentos , Esquema de Medicação , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/economia , Glucosídeos/administração & dosagem , Glucosídeos/economia , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/economia , Modelos Econométricos , Modelos Estatísticos , Metanálise em Rede , Anos de Vida Ajustados por Qualidade de Vida , Inibidores do Transportador 2 de Sódio-Glicose/economia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Espanha
5.
J Antimicrob Chemother ; 72(8): 2342-2350, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28575511

RESUMO

Objectives: To assess the population pharmacokinetics (popPK) of daptomycin at the conventional dose of 6 mg/kg/day in a cohort of oncohaematological patients. Methods: Patients underwent serial blood sampling on day 3 of therapy (before dosing and at 0, 0.5, 1, 2, 3, 5, 7, 9 and 12 h after dosing) to assess the pharmacokinetic profile of daptomycin. PopPK and Monte Carlo simulation were performed to define the probability of target attainment (PTA) with 6, 8, 10 and 12 mg/kg/day of the pharmacokinetic/pharmacodynamic target of AUC 24 /MIC >1081. Results: Thirty patients were recruited. A two-compartment open model with first-order intravenous input and first-order elimination was developed. Estimated creatinine clearance (CL CR ), serum albumin concentration (Alb) and presence of AML were covariates included in the final model. Monte Carlo simulation showed that the conventional 6 mg/kg/day dose resulted in optimal PTAs (≥80%) in the presence of pathogens with an MIC up to 0.5 mg/L only in patients with CL CR 50-100 mL/min/1.73 m 2 , Alb 26-45 g/L and a haematological diagnosis other than AML. Conversely, higher dosages, up to 12 mg/kg/day, were needed to achieve this goal in the presence of pathogens with an MIC of 0.25-0.5 mg/L in all of the other tested scenarios. In patients with CL CR 101-150 mL/min/1.73 m 2 and Alb 15-25 g/L, suboptimal PTAs (<60%) were predicted even with 12 mg/kg/day dosing . Conclusions: Our study provides a strong rationale for considering daptomycin dosages of ≥ 8 mg/kg/day in several clinical scenarios for oncohaematological patients. In some of these scenarios therapeutic drug monitoring could be a useful adjunct for optimized care.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Infecções Bacterianas/tratamento farmacológico , Daptomicina/administração & dosagem , Daptomicina/farmacocinética , Neoplasias Hematológicas/complicações , Adulto , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Plasma/química , Estudos Prospectivos
7.
Clin J Oncol Nurs ; 18 Suppl: 25-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25252988

RESUMO

Participation in the ONS Foundation-supported Breast Cancer Care Quality Measures Set pilot study was an opportunity for staff at a National Cancer Institute-designated comprehensive cancer center to improve their process for introducing a change in practice. The institution's treatment area revised a documentation tool, and the medical practice area embarked on an education project based on evidence-based practice from the Oncology Nursing Society's Putting Evidence Into Practice initiative. After implementation, an increase in the number of patients being assessed for the quality measures of fatigue and sleep-wake disturbances was noted. In addition, the number of patients being educated on neutropenia using evidence-based information increased.


Assuntos
Neoplasias da Mama/enfermagem , Avaliação em Enfermagem , Neoplasias da Mama/terapia , Enfermagem Baseada em Evidências , Feminino , Humanos , Liderança , Sociedades de Enfermagem
8.
FEBS J ; 281(17): 3844-54, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25040622

RESUMO

Proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) is an adaptor protein associated with the cytoskeleton that is mainly expressed in hematopoietic cells. Mutations in PSTPIP1 cause the rare autoinflammatory disease called pyogenic arthritis, pyoderma gangrenosum, and acne. We carried out this study to further our knowledge on PSTPIP1 function in T cells, particularly in relation to the phosphatase lymphoid phosphatase (LYP), which is involved in several autoimmune diseases. LYP-PSTPIP1 binding occurs through the C-terminal homology domain of LYP and the F-BAR domain of PSTPIP1. PSTPIP1 inhibits T-cell activation upon T-cell receptor (TCR) and CD28 engagement, regardless of CD2 costimulation. This function of PSTPIP1 depends on the presence of an intact SH3 domain rather than on the F-BAR domain, indicating that ligands of the F-BAR domain, such as the PEST phosphatases LYP and PTP-PEST, are not critical for its negative regulatory role in TCR signaling. Additionally, PSTPIP1 mutations that cause the pyogenic arthritis, pyoderma gangrenosum and acne syndrome do not affect PSTPIP1 function in T-cell activation through the TCR.


Assuntos
Acne Vulgar/genética , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Artrite Infecciosa/genética , Proteínas do Citoesqueleto/fisiologia , Pioderma Gangrenoso/genética , Receptores de Antígenos de Linfócitos T/fisiologia , Domínios de Homologia de src/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Antígenos CD28/fisiologia , Complexo CD3/fisiologia , Proteínas do Citoesqueleto/genética , Células HEK293 , Humanos , Células Jurkat , Ativação Linfocitária/efeitos dos fármacos , Proteína Tirosina Fosfatase não Receptora Tipo 22/fisiologia , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/fisiologia
9.
Breast Cancer Manag ; 3(6): 487-495, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26913082

RESUMO

This paper will present the multiple roles and the impact of cancer advocates. The emerging literature provides evidence for the consideration and integration of African American BC survivors as advocates in practice, policy and research relevant to cancer prevention and control. We present a practical outline for organizational assessment for the inclusion of advocates in these arenas. This assessment can be conducted by all levels of partners, including community advocacy and scientific organizations.

11.
J Pharm Sci ; 102(8): 2760-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23712859

RESUMO

An enhanced capacity for protoporphyrin IX (PpIX) synthesis through 5-aminolevulinic acid (ALA) administration has been reported in cancer cells. We compared the effect of ALA and ALA combined with gold nanoparticles (ALA-AuNPs) for photodynamic therapy (PDT) on human cervical cancer cell line. Because PpIX after photoactivation produces reactive oxygen species (ROS), ALA-AuNPs combinations can enhance this production and then induce higher phototoxicity. With this aim, two different-sized AuNPs (14 and 136 nm, AuNP1 and AuNP2, respectively) were successfully synthesized and characterized by UV-visible spectrophotometry and transmission electron microscopy. AuNPs were combined with ALA to evaluate their cooperative action in the intracellular ROS production, cell viability, and cell death mechanism. Results showed that ALA-AuNPs combinations induced cell death via ROS-mediated apoptosis after PDT. When exposed to light at their resonance wavelength, AuNP2 combined with ALA result in cytotoxicity and cell injury in greater extension than ALA and ALA-AuNP1 combination.


Assuntos
Ácido Aminolevulínico/farmacologia , Ouro/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Colo do Útero/efeitos dos fármacos , Colo do Útero/metabolismo , Colo do Útero/patologia , Sinergismo Farmacológico , Feminino , Ouro/química , Humanos , Nanopartículas/química , Nanopartículas/ultraestrutura , Fotoquimioterapia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
12.
J Cancer Surviv ; 7(3): 283-91, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23471728

RESUMO

PURPOSE: African-American breast cancer survivors (AABCS) suffer the greatest from cancer recurrence, morbidity, and mortality in part due to the lack of cancer follow-up care and surveillance. To improve survival and survivorship, the Institute of Medicine advises that cancer survivors be provided a survivorship care plan (SCP). The current study investigated AABCS' understanding of SCP and gathered preliminary feedback on infusing cultural and socioecological responsiveness. METHODS: The study embraced a community-based participatory research framework. Three facilitated, structured, consensus meetings were conducted with AABCS (N = 25) and advocates (N = 3) to provide information towards identifying the content domains of an SCP that are culturally responsive to AABCS. RESULTS: AABCS recommended inclusion of patient-centered information on the purpose and use of the SCP. They raised concerns that higher mortality in AABCS may be due to greater comorbidities and inadequate surveillance and follow-up care. Participants recommended that the SCP document all comorbidities and medications, regardless of relationship to cancer; referrals for cancer-related providers; and culturally informed health advisories. CONCLUSION: Study findings indicate that the available SCP template lacked adequate content on health history, comorbidity, health promotion, and functioning. These factors constitute the underlying clinical, psychosocial, and behavioral risks for poor disease outcomes that may be exacerbated in AABCS. IMPLICATIONS FOR CANCER SURVIVORS: SCPs are intended to educate and activate patients to join their oncology care team as informed partners. However, the emerging science and implementation of SCPs seem void of patient input. Our investigation suggests a practical approach for survivor engagement in the SCP discourse to increase their cultural responsiveness and patient-centeredness.


Assuntos
Negro ou Afro-Americano/psicologia , Neoplasias da Mama/etnologia , Necessidades e Demandas de Serviços de Saúde , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Planejamento de Assistência ao Paciente , Sobreviventes , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/psicologia , Neoplasias da Mama/reabilitação , Feminino , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Defesa do Paciente/psicologia , Defesa do Paciente/estatística & dados numéricos , Planejamento de Assistência ao Paciente/normas , Planejamento de Assistência ao Paciente/estatística & dados numéricos , Relações Médico-Paciente , Taxa de Sobrevida , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricos
13.
Oncol Nurs Forum ; 39(6): 585-91, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23107852

RESUMO

PURPOSE/OBJECTIVES: To examine the impact of support groups among African American breast cancer survivors (BCSs). RESEARCH APPROACH: A qualitative research study. SETTING: Community health and cancer centers and churches. PARTICIPANTS: 62 African American BCSs. METHODOLOGIC APPROACH: Focus groups were conducted with African American BCSs to share their experiences with peer-based support groups. A brief questionnaire was administered and assessed demographics, medical history, and support group impact. FINDINGS: Survivors emphasized that a culturally embedded focus was essential for their participation in a cancer support group. The survivors underscored that cultural-based groups are rooted in the spiritual, linguistic, experiential, and historical contexts of the intended constituents. The peer-based support groups provided multilevel functions, including emotional, social, spiritual, informational, and financial support, as well as patient navigation. The groups' activities fostered personal development and a call to community advocacy that included prevention education and research engagement. CONCLUSIONS: The unique strengths of grassroots community-based support groups are that they are culturally consonant, peer-based, and responsive to cancer-related and personal needs. The contribution and value of those multifaceted peer-based groups expand the paradigm of supportive care, extending the net of psychosocial care to underserved and underrepresented cancer survivors. INTERPRETATION: Research provides the critical foundation to lead and articulate the studies necessary to bridge peer- and professional-based care to ensure the psychosocial needs of increasingly diverse survivors are met.


Assuntos
Negro ou Afro-Americano , Neoplasias da Mama , Grupo Associado , Grupos de Autoajuda , Sobreviventes , Adulto , Neoplasias da Mama/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Enfermagem , Inquéritos e Questionários
14.
Brain Pathol ; 22(5): 636-53, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22188425

RESUMO

Double-transgenic amyloid precursor protein/presenilin 1 (APP/PS1) mice express a chimeric mouse/human APP bearing the Swedish mutation (Mo/HuAPP695swe) and a mutant human PS1-dE9 both causative of familial Alzheimer's disease (FAD). Transgenic mice show impaired memory and learning performance from the age of 6 months onwards. Double-transgenic APP/PS1 mice express altered APP and PS1 mRNAs and proteins, reduced ß-secretase 1 (BACE1) mRNA and normal BACE1 protein, all of which suggest a particular mechanism of amyloidogenesis when compared with sporadic AD. The first ß-amyloid plaques in APP/PS1 mice appear at 3 months, and they increase in number and distribution with disease progression in parallel with increased levels of brain soluble ß-amyloid 1-42 and 1-40, but also with reduced 1-42/1-40 ratio with age. Amyloid deposition in plaques is accompanied by altered mitochondria and increased oxidative damage, post-translational modifications and accumulation of altered proteins at the dystrophic neurites surrounding plaques. Degradation pathways are also modified with disease progression including activation of the immunoproteasome together with variable alterations of the different protease activities of the ubiquitin-proteasome system. Present observations show modifications in the production of ß-amyloid and activation and malfunction of the subcellular degradation pathways that have general implications in the pathogenesis of AD and more particularly in specificities of FAD amyloidogenesis.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Transtornos Cognitivos/etiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Fatores Etários , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Aprendizagem da Esquiva/fisiologia , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/ultraestrutura , Cisteína Endopeptidases/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Regulação da Expressão Gênica/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Eletrônica de Transmissão , Microscopia Imunoeletrônica , Proteínas Quinases Ativadas por Mitógeno , Mutação/genética , Testes Neuropsicológicos , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Placa Amiloide/ultraestrutura , Presenilina-1/genética , Complexo de Endopeptidases do Proteassoma/genética , RNA Mensageiro/metabolismo , Reconhecimento Psicológico/fisiologia , Transdução de Sinais/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Ubiquitina Tiolesterase/metabolismo , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismo
15.
Phys Chem Chem Phys ; 13(28): 13026-33, 2011 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-21691659

RESUMO

By comparison and combination of two strategies, extending π-conjugation and tuning Intramolecular Charge Transfer (ICT) effect, new long-wavelength BODIPY dyes have been efficiently synthesized. The new chromophores exhibit good optical properties: high fluorescence quantum yields, exceptionally large molar extinction coefficients, narrow red-emission bands, and relatively large Stokes shifts etc., in polar or apolar solvents. Besides, the new dyes, under transversal pumping at 532 nm, exhibit highly efficient and stable laser emission tunable from the green to NIR spectral region (570-725 nm). Moreover, one of these new BODIPY derivatives shows cell membrane permeability and bright intracellular red fluorescence. These advantageous characteristics assure the potential of these dyes for biophotonic applications.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Lasers de Corante , Óptica e Fotônica , Acetatos/química , Acetona/química , Acetonitrilas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citoplasma/metabolismo , Eletroquímica , Etanol/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/metabolismo , Corantes Fluorescentes/farmacologia , Hexanos/química , Humanos , Lasers de Estado Sólido , Metanol/química , Cloreto de Metileno/química , Modelos Moleculares , Estrutura Molecular , Fotólise/efeitos da radiação , Teoria Quântica , Solventes/química , Espectrometria de Fluorescência , Espectrofotometria , Trifluoretanol/química
16.
Thyroid ; 20(5): 563-7, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20450434

RESUMO

BACKGROUND: Cerebellar metastasis (CM) from papillary thyroid carcinoma (PTC) is exceptional with only 12 reported cases and usually carries a very poor prognosis. In the two previously reported patients in whom CM was detected before PTC, other distant or local metastases were already present by the time of PTC diagnosis. We report a patient found to have papillary thyroid microcarcinoma after surgical resection and histopathological study of a large solitary hemorrhagic CM, who showed no evidence of other metastatic sites and survived 7 years after initial diagnosis. SUMMARY: A 65-year-old female patient with a history of surgical resection of a 7-cm cerebellar mass diagnosed with PTC metastasis, and adjuvant treatment with cranial external radiotherapy, was referred to us. The neck ultrasonography showed a solitary 4-mm right thyroid nodule. Histopathology after total thyroidectomy revealed a 2-mm papillary thyroid microcarcinoma, sclerosing variant, with capsule infiltration but no regional lymph node invasion. Although she received a total dose of 500 mCi of 131-I after surgery and the last two whole-body scans were normal, serum thyroglobulin levels progressively increased. The patient refused any further test or treatment other than basal blood sampling and suppressive therapy with levothyroxine and remained stable for 4 years until she started to complain about deviation of her walk. A computed tomography scan showed a regrowth of the metastasis. She suffered a sudden worsening of her neurological status because of a big intratumoral hemorrhage that required decompressive craniectomy and hematoma evacuation surviving 3 years more after this episode. CONCLUSIONS: To our knowledge, this is the first reported case of a solitary CM from an occult PTC, and also the first that developed an acute cerebellar hemorrhage years after cranial surgery, however, exhibiting the longest reported survival. This case highlights the importance of not only an appropriate initial treatment of the CM and primary PTC in these patients, but also a close follow-up, to avoid further complications and improve their prognosis.


Assuntos
Carcinoma Papilar/patologia , Carcinoma Papilar/secundário , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/secundário , Hemorragia Cerebral/etiologia , Neoplasias da Glândula Tireoide/patologia , Idoso , Carcinoma Papilar/cirurgia , Neoplasias Cerebelares/cirurgia , Hemorragia Cerebral/patologia , Hemorragia Cerebral/terapia , Terapia Combinada , Craniotomia , Evolução Fatal , Feminino , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Tireoidectomia , Tomografia Computadorizada por Raios X , Ultrassonografia , Imagem Corporal Total
17.
J Alzheimers Dis ; 19(2): 489-502, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20110596

RESUMO

Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.


Assuntos
Doença de Alzheimer/patologia , Córtex Cerebral/ultraestrutura , Lipídeos/química , Microdomínios da Membrana/metabolismo , Adenosina Trifosfatases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Análise de Variância , Caveolina 1/metabolismo , Córtex Cerebral/patologia , Clatrina/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Feminino , Humanos , Lipídeos/análise , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Adulto Jovem
18.
Arch Dermatol ; 146(1): 39-45, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20083691

RESUMO

OBJECTIVE: To analyze the absorption of tattoo inks related to their in vivo and in vitro behavior under laser irradiation to improve laser-assisted tattoo removal. DESIGN: The absorption of 21 tattoo inks in a wavelength range from 300 to 800 nm was characterized by reflection spectroscopy from samples consisting of inks mixed in gelatin. Tattoo inks were removed in vitro using pulsed laser radiation with different variables, and morphologic analysis of the irradiated areas was performed. SETTING: An interdisciplinary laser laboratory with a common industrial project with the Spanish company Milesman S.A. PARTICIPANT: One person was voluntarily tattooed with 2 of the studied inks. MAIN OUTCOME MEASURES: (1) First approach to the optimum dose for pigment removal in in vitro models. (2) Correlation between the in vitro and in vivo situations at the optimum dose. RESULTS: Reflection spectroscopy facilitated selection of the most adequate laser wavelengths for tattoo removal. Red, orange, and rose inks were successfully lightened at 532 nm with 0.6 J/cm2; brown at 1064 nm with 0.3 J/cm2; yellow and green at 448 nm with 2.6 J/cm2; and blue at 600 nm with 0.9 J/cm2. Similar colors in in vitro and in vivo tattoos responded with the same efficiency to the laser variables. CONCLUSIONS: High efficiency is reached in the removal of in vivo tattoos by using an irradiation wavelength at which the percentage of reflection from the pigment is minimal. Under this condition, laser pulses can be used with a low fluence, minimizing adverse effects and clinical time.


Assuntos
Terapia com Luz de Baixa Intensidade/métodos , Tatuagem , Humanos , Modelos Biológicos , Pigmentos Biológicos
19.
Clin J Oncol Nurs ; 11(2): 201-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17573269

RESUMO

Ovarian cancer is the most lethal gynecologic cancer. Early-stage diagnosis is difficult, and chemotherapy treatments often are not durable. Despite challenges, progress has been made since the 1990s; healthcare professionals now have an increased understanding of the disease biology and can identify hereditary ovarian cancer and provide screening recommendations. The recognized importance of complete staging, cytoreductive surgery, and new effective treatments has made an improvement in five-year survival.


Assuntos
Neoplasias Ovarianas/terapia , Quimioterapia Adjuvante , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/tratamento farmacológico , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Fatores de Risco
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