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1.
Rheumatol Int ; 43(12): 2245-2250, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37697044

RESUMO

Anti-carbamylated protein (anti-CarP) antibodies are promising biomarkers in rheumatoid arthritis (RA), although their significance in seronegative disease (SNRA) remains uncertain. To assess the influence of anti-CarP antibodies on disease activity and erosive joint damage in SNRA patients. In RA patients, rheumatoid factor (RF), anti-citrullinated protein antibodies, and anti-CarP antibodies were measured. Disease activity was assessed using DAS28-CRP and SDAI indices, while musculoskeletal ultrasound identified bone erosions. A total of 77 patients were enrolled, comprising 49 with seropositive RA (SPRA) and 28 with SNRA. Notably, 28% of SPRA and 10% of SNRA patients were positive to anti-CarP antibodies. Anti-CarP-positive patients exhibited elevated C-reactive protein (median 10.6, interquartile range 4.6-20.0 vs. 3.4, 1.7-9.9 mg/L; p = 0.005), erythrocyte sedimentation rate (34, 19-46 vs. 16, 7-25 mm/h; p = 0.002), DAS28-CRP (3.2, 2.6-4.2 vs. 2.6, 1.9-3.5; p = 0.048), and SDAI (19.9, 6.3-32.1 vs. 10.9, 5.5-18.1; p = 0.034) indices. Multivariate analysis revealed RF positivity as the sole predictor for anti-CarP antibodies (odds ratio [OR] = 5.9). Musculoskeletal ultrasound revealed bone erosions in 36% of RA patients; 35% among anti-CarP-negative patients and 40% among anti-CarP-positive patients. Notably, RF presence (OR = 44.3) and DAS28-CRP index (OR = 2.4) emerged as predictors of musculoskeletal ultrasound-confirmed erosive joint disease. Anti-CarP antibodies are detected at similar frequencies among both SPRA and SNRA patients. While associated with increased disease activity, these antibodies did not correlate with increased erosive joint damage.

2.
J Clin Rheumatol ; 27(6S): S274-S277, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32028304

RESUMO

BACKGROUND: Spread of complex regional pain syndrome (CRPS) outside the affected limb is a well-recognized phenomenon; nevertheless, the actual evolution from CRPS to fibromyalgia is poorly documented. Similar mechanisms have been recently put forward to explain the development of CRPS and fibromyalgia including dorsal root ganglia (DRG) hyperexcitability and small fiber neuropathy. OBJECTIVES: The aims of this study were to describe 3 cases with typical CRPS evolving to full-blown fibromyalgia and to discuss the potential pathogenetic mechanisms linking these debilitating illnesses. METHODS: This was a review of medical records and PubMed search on the relationship between CRPS-fibromyalgia with DRG and small nerve fiber neuropathy. RESULTS: Our 3 cases displayed over time orderly evolution from CRPS to fibromyalgia. Dorsal root ganglion hyperexcitability and small fiber neuropathy have been recently demonstrated in CRPS and in fibromyalgia. Dorsal root ganglia contain the small nerve fiber cell bodies surrounded by glial cells. After trauma, DRG perineuronal glial cells produce diverse proinflammatory mediators. Macrophages, lymphocytes, and satellite glial cells may drive the immune response to more rostrally and caudally located DRG and other spinal cord sites. Dorsal root ganglion metabolic changes may lead to small nerve fiber degeneration. This mechanism may explain the development of widespread pain and autonomic dysfunction. CONCLUSIONS: Clinicians should be aware that CRPS can evolve to full-blown fibromyalgia. Spreading of neuroinflammation through DRG glial cell activation could theoretically explain the transformation from regional to generalized complex pain syndrome.


Assuntos
Síndromes da Dor Regional Complexa , Fibromialgia , Síndromes da Dor Regional Complexa/diagnóstico , Síndromes da Dor Regional Complexa/etiologia , Fibromialgia/diagnóstico , Gânglios Espinais , Humanos , Dor , Manejo da Dor
3.
Curr Opin Anaesthesiol ; 32(5): 649-652, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31415045

RESUMO

PURPOSE OF REVIEW: The clinical practice of anesthesia continues to evolve and grow toward increasing quality and safety while improving the patient and family perioperative experience. Within the realm of pediatric anesthesia, advances in regional anesthesia techniques are important part in this aim. RECENT FINDINGS: The aim of this review is to provide an update on recent advances in pediatric regional anesthesia. This includes an emphasis on safety data from large datasets that previously were not available. In addition, novel blocks within pediatric regional anesthesia will be described. SUMMARY: Large data sets have given clinical providers information into the practice of regional anesthesia. It has confirmed the safety of common regional anesthetic techniques in addition to providing guidance to improving outcomes for children.


Assuntos
Anestesia por Condução/métodos , Anestésicos Locais/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Fatores Etários , Anestesia por Condução/efeitos adversos , Anestesia por Condução/normas , Anestesiologia/métodos , Anestesiologia/normas , Anestésicos Locais/efeitos adversos , Criança , Conjuntos de Dados como Assunto , Europa (Continente) , Humanos , Dor Pós-Operatória/etiologia , Guias de Prática Clínica como Assunto , Sociedades Médicas/normas , Resultado do Tratamento , Estados Unidos
4.
J Clin Rheumatol ; 20(3): 146-50, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24662556

RESUMO

BACKGROUND: Fibromyalgia often coexists and overlaps with other syndromes such as chronic fatigue, irritable bowel syndrome, and interstitial cystitis. Chronic stress has been implicated in the pathogenesis of these illnesses. The sympathetic nervous system is a key element of the stress response system. Sympathetic dysfunction has been reported in these syndromes, raising the possibility that such dysautonomia could be their common clustering underlying pathogenesis. OBJECTIVE: The objective of this study was to carry out a review of all published comparative case-control studies investigating sympathetic nervous system performance in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. METHODS: Online databases PubMed and EMBASE were accessed using the following key words: autonomic (OR) sympathetic (AND) fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. All entries up to December 10th 2012 were reviewed by 2 independent investigators searching for case-control studies in humans. The Method for Evaluating Research and Guidelines Evidence adapted to the Scottish Intercollegiate Guidelines Network was used to rank the level of evidence contained in the selected articles. RESULTS: A total of 196 articles are included in this review. The most often used methods to assess sympathetic functionality were heart rate variability analysis, sympathetic skin response, tilt table testing, and genetic studies. The majority of studies (65%) described sympathetic nervous system predominance in these overlapping syndromes. In contrast, 7% of the studies found parasympathetic predominance. CONCLUSIONS: This review demonstrates that sympathetic nervous system predominance is common in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. This concordance raises the possibility that sympathetic dysfunction could be their common underlying pathogenesis that brings on overlapping clinical features. The recognition of sympathetic predominance in these 4 syndromes may have potential clinical implications. It may be worth exploring the use of nonpharmacological measures as well as drug therapies aimed to regain autonomic balance.


Assuntos
Cistite Intersticial/fisiopatologia , Síndrome de Fadiga Crônica/fisiopatologia , Fibromialgia/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Estudos de Casos e Controles , Frequência Cardíaca/fisiologia , Humanos , Pele/inervação , Estresse Fisiológico/fisiologia , Teste da Mesa Inclinada
5.
Reg Anesth Pain Med ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38925711

RESUMO

BACKGROUND: Nerve block utility has been extensively described in the operating room, however, there is a paucity of evidence regarding blocks in the interventional radiology (IR) suite, with no studies examining its safety and efficacy in children. METHODS: A retrospective study was conducted at a single tertiary-care children's hospital to evaluate the analgesic utility of nerve blocks during IR-performed sclerotherapy for bone cysts, venous malformations, and lymphatic malformations. Lymphatic and venous malformations were combined for final analysis. Patients between January 2016 and September 2022 had their medical records reviewed for procedural data, postprocedural pain scores, and analgesic administration data. RESULTS: 309 patients were included in the final analysis. Opioids were required significantly less frequently intraprocedurally and postprocedurally across subgroups. The proportion of patients who received opioids during their hospital course was significant between block and non-block patients, respectively: bone cyst: 62.7% vs 100% (p<0.001); venous and lymphatic malformation: 65.7% vs 97.4% (p<0.001). Average maximum postanesthesia care unit (PACU) pain scores were significantly lower in bone cyst patients with no significant difference seen in pain scores among venous and lymphatic malformation patients. There were no reported nerve block-related complications. DISCUSSION: Nerve blocks demonstrated an opioid-sparing effect intraprocedurally and postprocedurally for all subgroups. Their use among bone cyst patients was associated with significant reductions in average maximum PACU pain scores. Nerve blocks may constitute an effective opioid-sparing component of multimodal analgesia in pediatric patients undergoing IR sclerosis procedures. Prospective data are needed to establish the optimal utility of nerve blocks in the IR setting.

6.
Am J Ind Med ; 56(1): 111-23, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22619114

RESUMO

BACKGROUND: The study of workers' health problems possibly associated with stressful conditions requires valid and reliable tools for monitoring risk factors. The present study validates two questionnaires to assess psychosocial risk factors for stress-related illnesses within a sample of Colombian workers. METHODS: The validation process was based on a representative sample survey of 2,360 Colombian employees, aged 18-70 years. Worker response rate was 90%; 46% of the responders were women. Internal consistency was calculated, construct validity was tested with factor analysis and concurrent validity was tested with Spearman correlations. RESULTS: The questionnaires demonstrated adequate reliability (0.88-0.95). Factor analysis confirmed the dimensions proposed in the measurement model. Concurrent validity resulted in significant correlations with stress and health symptoms. CONCLUSIONS: "Work and Non-work Psychosocial Factors Questionnaires" were found to be valid and reliable for the assessment of workers' psychosocial factors, and they provide information for research and intervention.


Assuntos
Estresse Psicológico/etiologia , Inquéritos e Questionários , Local de Trabalho/psicologia , Adolescente , Adulto , Idoso , Colômbia , Análise Fatorial , Feminino , Humanos , Liderança , Masculino , Pessoa de Meia-Idade , Autonomia Profissional , Psicometria , Reprodutibilidade dos Testes , Recompensa , Fatores de Risco , Apoio Social , Estatísticas não Paramétricas , Carga de Trabalho , Adulto Jovem
7.
Am J Ind Med ; 56(1): 100-10, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22628068

RESUMO

BACKGROUND: Evaluation of psychosocial factors requires instruments that measure dynamic complexities. This study explains the design of a set of questionnaires to evaluate work and non-work psychosocial risk factors for stress-related illnesses. METHODS: The measurement model was based on a review of literature. Content validity was performed by experts and cognitive interviews. Pilot testing was carried out with a convenience sample of 132 workers. Cronbach's alpha evaluated internal consistency and concurrent validity was estimated by Spearman correlation coefficients. RESULTS: Three questionnaires were constructed to evaluate exposure to work and non-work risk factors. Content validity improved the questionnaires coherence with the measurement model. Internal consistency was adequate (α = 0.85-0.95). Concurrent validity resulted in moderate correlations of psychosocial factors with stress symptoms. CONCLUSIONS: Questionnaires' content reflected a wide spectrum of psychosocial factors sources. Cognitive interviews improved understanding of questions and dimensions. The structure of the measurement model was confirmed.


Assuntos
Estresse Psicológico/etiologia , Inquéritos e Questionários , Local de Trabalho/psicologia , Adolescente , Adulto , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Psicometria , Reprodutibilidade dos Testes , Fatores de Risco , Estatísticas não Paramétricas , Adulto Jovem
8.
Children (Basel) ; 10(8)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37628373

RESUMO

Various regional anesthetics have been used for postoperative analgesia for pediatric craniotomy. In this case series, we report retrospectively collected data on postoperative pain and analgesic use in 44 patients who received ultrasound-guided occipital nerve blocks in addition to intravenous analgesic agents for posterior craniotomy procedures. In the immediate post-anesthesia care unit, pain was rated as zero or well controlled in 77% of patients, with only 43% requiring intravenous or demand patient-controlled analgesia opioids. There were no block-related complications. Occipital nerve blocks may constitute a safe and effective component of multimodal analgesia in this population.

9.
BMC Musculoskelet Disord ; 13: 23, 2012 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-22348792

RESUMO

BACKGROUND: A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM); and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG) are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7) act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms. METHODS: We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP) were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637. RESULTS: The frequency of the rs6754031 polymorphism was significantly different in both groups (P = 0.036) mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88) than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; P = 0.002) and the TT genotype (median = 71; percentile 25/75 = 64/77; P = 0.001). CONCLUSION: In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that some patients with severe FM may have a dorsal root ganglia sodium channelopathy.


Assuntos
Fibromialgia/genética , Gânglios Espinais/patologia , Polimorfismo Genético/genética , Índice de Gravidade de Doença , Canais de Sódio/genética , Adulto , Estudos de Casos e Controles , Feminino , Fibromialgia/epidemiologia , Fibromialgia/etnologia , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Canal de Sódio Disparado por Voltagem NAV1.7 , Nociceptores/patologia
10.
Nat Cancer ; 3(3): 318-336, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35122074

RESUMO

KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) is highly immunosuppressive and resistant to targeted and immunotherapies. Among the different PDAC subtypes, basal-like mesenchymal PDAC, which is driven by allelic imbalance, increased gene dosage and subsequent high expression levels of oncogenic KRAS, shows the most aggressive phenotype and strongest therapy resistance. In the present study, we performed a systematic high-throughput combination drug screen and identified a synergistic interaction between the MEK inhibitor trametinib and the multi-kinase inhibitor nintedanib, which targets KRAS-directed oncogenic signaling in mesenchymal PDAC. This combination treatment induces cell-cycle arrest and cell death, and initiates a context-dependent remodeling of the immunosuppressive cancer cell secretome. Using a combination of single-cell RNA-sequencing, CRISPR screens and immunophenotyping, we show that this combination therapy promotes intratumor infiltration of cytotoxic and effector T cells, which sensitizes mesenchymal PDAC to PD-L1 immune checkpoint inhibition. Overall, our results open new avenues to target this aggressive and therapy-refractory mesenchymal PDAC subtype.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pancreáticas/tratamento farmacológico , Microambiente Tumoral
11.
Psychol Psychother ; 93(3): 474-489, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31246370

RESUMO

OBJECTIVE: Borderline personality disorder (BPD) consists of a persistent pattern of instability in affective regulation, impulse control, interpersonal relationships, and self-image. Although certain forms of psychotherapy are effective, their effects are small to moderate. One of the strategies that have been proposed to improve interventions involves integrating the therapeutic elements of different psychotherapy modalities from a contextual behavioural perspective (ACT, DBT, and FAP). METHODS: Patients (n = 65) attending the BPD Clinic of the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñíz in Mexico City who agreed to participate in the study were assigned to an ACT group (n = 22), a DBT group (n = 20), or a combined ACT + DBT + FAP therapy group (n = 23). Patients were assessed at baseline and after therapeutic trial on measures of BPD symptom severity, emotion dysregulation, experiential avoidance, attachment, control over experiences, and awareness of stimuli. RESULTS: ANOVA analyses showed no differences between the three therapeutic groups in baseline measures. Results of the MANOVA model showed significant differences in most dependent measures over time but not between therapeutic groups. CONCLUSIONS: Three modalities of brief, contextual behavioural therapy proved to be useful in decreasing BPD symptom severity and emotional dysregulation, as well as negative interpersonal attachment. These changes were related to the reduction of experiential avoidance and the acquisition of mindfulness skills in all treatment groups, which may explain why no differences between the three different intervention modalities were observed. PRACTITIONER POINTS: Brief adaptations of acceptance and commitment therapy and dialectical behavioural therapy are effective interventions for BPD patients, in combined or isolated modalities, and with or without the inclusion of functional analytic psychotherapy. The reduction of experiential avoidance and the acquisition of mindfulness skills are related with the diminution of BPD symptoms severity, including emotional dysregulation and negative interpersonal attachment.


Assuntos
Terapia de Aceitação e Compromisso/métodos , Transtorno da Personalidade Borderline/terapia , Terapia do Comportamento Dialético/métodos , Terapia Psicanalítica/métodos , Adulto , Transtorno da Personalidade Borderline/psicologia , Emoções , Feminino , Humanos , Masculino , Atenção Plena/métodos , Psicoterapia de Grupo/métodos , Resultado do Tratamento , Adulto Jovem
12.
J Clin Rheumatol ; 15(4): 172-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19342959

RESUMO

BACKGROUND: It has been suggested that autonomic nervous system dysfunction may explain all of fibromyalgia (FM) multisystem features. Such proposal is based mostly on the results of diverse heart rate variability analyses. The Composite Autonomic Symptom Scale (COMPASS) is a different validated method to recognize dysautonomia. OBJECTIVES: The main objective of our study was to investigate symptoms of autonomic dysfunction in FM patients by means of COMPASS. A secondary objective was to define whether there is a correlation between COMPASS and Fibromyalgia Impact Questionnaire (FIQ) scores in FM patients. METHODS: Design, analytical cross-sectional study. Our study population included 3 different groups of women: 30 patients with FM, 30 patients with rheumatoid arthritis, and 30 women who considered themselves healthy. All participants filled out COMPASS and FIQ questionnaires. RESULTS: FM patients had significantly higher values in all COMPASS domains. COMPASS total score (54.6 +/- 20.9; mean +/- standard deviation) clearly differentiated FM patients from the other 2 groups (21.6 +/- 16.5 and 9.5 +/- 10.2, respectively). P < 0.0001. The majority of FM patients gave affirmative answers to questions related to orthostatic, digestive, sleep, sudomotor, or mucosal dysfunction. There was a significant correlation between COMPASS and FIQ scores (Spearman r = 0.5, P < 0.005). CONCLUSIONS: Patients with FM have multiple nonpain symptoms related to different expressions of autonomic dysfunction. There is a correlation between a questionnaire that measures FM severity (FIQ) and an autonomic dysfunction questionnaire (COMPASS). Such correlation suggests that autonomic dysfunction is inherent to FM.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Fibromialgia/fisiopatologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto , Artrite Reumatoide/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Avaliação da Deficiência , Feminino , Nível de Saúde , Humanos , Pessoa de Meia-Idade
13.
J Psychiatr Res ; 114: 126-132, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31071663

RESUMO

Emotional dysregulation is one of the main features of Borderline Personality Disorder (BPD). Therefore, it constitutes a central therapeutic objective of the interventions that have proven to be effective for these patients, including the Acceptance and Commitment Therapy (ACT). However, benefits on emotional regulation have been evaluated through self-report instruments, and an anatomically based, objective, and precise measurement of the ability to change the type, duration and frequency of emotions is still needed. OBJECTIVE: To assess facial emotion expression, valence and arousal during an ACT based intervention, between initial, middle and final therapeutic sessions for BPD patients. METHOD: Using the FaceReader 7.0, 29 recordings of individual therapeutic sessions for BPD patients during an ACT intervention trial were analyzed. RESULTS: Happiness and fear intensity increase from the beginning to the end of the sessions, while sadness decreases. Emotional valence exhibits a significant decrease in its negative value during sessions from -0.13 (S.D. = 0.12) at the initial part of the sessions to -0.06 (S.D. = 0.08) by the end of the sessions, with a moderate effect size (Cohen d = 0.69). Emotional arousal increased from the beginning to the end of sessions and whole intervention. CONCLUSION: The emotional valence and arousal differed according to the psychotherapeutically process involved during ACT intervention, suggesting that the systematic analysis of facial expressions allows a rigorously examination of the relations between emotions, physiological processes, and instrumental behavior experimented though a psychotherapeutically process.


Assuntos
Terapia de Aceitação e Compromisso , Transtorno da Personalidade Borderline/terapia , Expressão Facial , Terapia de Aceitação e Compromisso/métodos , Adulto , Transtorno da Personalidade Borderline/psicologia , Emoções Manifestas , Feminino , Humanos , Masculino , Adulto Jovem
14.
Eur J Pharm Biopharm ; 69(1): 1-9, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-17826969

RESUMO

Polymeric drug-loaded nanoparticles have been extensively studied in the field of drug delivery. Biodistribution depends on the physicochemical properties of particles, especially size. The global message from the literature is that small particles have an enhanced ability to reach their target. The present review highlights the difficulties in validating the data from biodistribution studies without accurate particle size determination.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas/química , Animais , Química Farmacêutica , Portadores de Fármacos , Indústria Farmacêutica/tendências , Humanos , Nanomedicina , Nanoestruturas/química , Nanotecnologia/métodos , Tamanho da Partícula , Polímeros/química , Solubilidade , Propriedades de Superfície , Tecnologia Farmacêutica
15.
Eur J Pharm Biopharm ; 69(1): 43-53, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18023564

RESUMO

Encapsulation of hydrophobic photosensitizers (PS) into polymeric nanoparticles (NP) has proven to be an effective alternative to organic solvents for their formulation. As NP size controls NP passage through endothelial barriers, it is a key parameter for achieving passive targeting of cancer tissues and choroidal neovascularization, secondary to age-related macular degeneration, the main applications of photodynamic therapy. In the present study, a hydrophobic PS, the meso-tetra(p-hydroxyphenyl)porphyrin, was encapsulated into biodegradable NP made of poly(D,L-lactide-co-glycolide) 50:50 via an emulsification-diffusion technique. NP batches having mean diameters of 117, 285, and 593 nm were obtained with narrow size distribution. Using the chorioallantoic membrane (CAM) of the developing chick embryo, it was demonstrated that the increase in the NP size decreased photodynamic activity in vivo. The activity of PS-loaded NP was not influenced by the volume of injection and was kept intact at least 6h after NP reconstitution. Investigation of NP circulation after IV administration by fluorescence measurements revealed that 117 nm NP reached Tmax earlier than larger NP. Confocal imaging of CAM vessels demonstrated PS uptake by endothelial cells after NP administration. It was concluded that NP size controls the photodynamic activity of the encapsulated PS.


Assuntos
Nanopartículas/química , Fotoquimioterapia/instrumentação , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Animais , Química Farmacêutica/métodos , Galinhas , Membrana Corioalantoide/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Degeneração Macular/metabolismo , Microscopia Confocal , Nanotecnologia/métodos , Rodaminas/química , Tecnologia Farmacêutica/métodos , Resultado do Tratamento
16.
Expert Rev Med Devices ; 15(12): 911-927, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30451031

RESUMO

INTRODUCTION: Structural and physiologic differences between pediatric and adult patients make management of the pediatric airway a challenge. Many initial airway device designs were modeled for adult patients and simply downsized for the pediatric population. This paper reviews the last decade's design improvements in video laryngoscopes and supraglottic airway devices (SGAs), as well as advances in noninvasive oxygenation/ventilation techniques for pediatric airway management. AREAS COVERED: Topic areas reviewed include basic principles of common and newer devices for video laryngoscopy, supraglottic airway management, and alternate ventilation techniques. A literature search was conducted in PubMed using device-specific keywords and limited to neonatal, infant, and pediatric populations. Articles were reviewed for evidence deemed high yield by the authors. Device specifications were obtained from manufacturer correspondences. Features, comparisons, advantages, and disadvantages are provided for each device class. We give expert commentary regarding the current state of clinical application, research considerations, as well as a 5-year outlook on potential areas of device design and development. EXPERT COMMENTARY: Video laryngoscopes and SGAs are safe and effective for use in children and improvements continue to be made for neonates and infants. The most significant area of new research is in the area of noninvasive airway devices for oxygenation and ventilation in difficult airways.


Assuntos
Manuseio das Vias Aéreas/instrumentação , Manuseio das Vias Aéreas/tendências , Criança , Desenho de Equipamento , Humanos , Intubação Intratraqueal/instrumentação , Laringoscópios , Oxigênio/análise , Ventilação
17.
Adv Drug Deliv Rev ; 59(11): 1162-76, 2007 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-17870202

RESUMO

Mammalian models are frequently used for preclinical evaluation of new drug delivery systems (DDS). However, valid mammalian models are expensive, time-consuming, and not easy to set up and evaluate. Furthermore, they are often linked to administrative burden with respect to ethical and legal aspects. The present review outlines the possibilities and limitations of using the hen's embryo, and specifically its chorioallantoic membrane (CAM), as an alternative to mammalian models for the evaluation of DDS. Features of the CAM, the anatomy of the embryo, and the blood were investigated to assess properties of the drug carriers such as toxicity and biocompatibility, as well as the activity, toxicity, biodistribution and pharmacokinetics of the drug. The simplicity, rapidity, and low cost of the different assays that can be performed with chick embryos strengthen the interest of routinely using this model in pharmaceutical technology research. It is concluded that there is a big potential for using chick embryos in screening procedures of formulation candidates, thus establishing an intermediate step between in vitro cellular tests and preclinical mammalian models.


Assuntos
Embrião de Galinha/efeitos dos fármacos , Membrana Corioalantoide/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Inibidores da Angiogênese/farmacologia , Animais , Técnicas Biossensoriais , Química Farmacêutica , Embrião de Galinha/metabolismo , Membrana Corioalantoide/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Fármacos Fotossensibilizantes/farmacologia , Distribuição Tecidual
18.
J Nucl Cardiol ; 14(4): 566-72, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17679066

RESUMO

BACKGROUND: There is limited knowledge about endothelial dysfunction in patients with primary antiphospholipid syndrome (PAPS). The purpose of this study was to evaluate endothelial function in patients with PAPS assessed by positron emission tomography. METHODS AND RESULTS: A 3-phase protocol--rest, cold pressor test (CPT), and adenosine positron emission tomography with nitrogen 13 ammonia--was used in 18 patients with PAPS and 18 healthy volunteers (HVs). Myocardial blood flow (MBF) was measured in each phase, with calculation of the endothelial-dependent vasodilation index, the increase in the MBF in response to CPT, and the myocardial flow reserve. An important trend was found in the myocardial flow reserve (2.76 +/- 1.04 in PAPS group vs 3.27 +/- 0.72 in HV group, P > .05), in the endothelial-dependent vasodilation index (1.19 +/- 0.31 in PAPS group vs 1.55 +/- 0.37 in HV group, P < .05), and in the percent change in the MBF in response to CPT (from rest) (19% +/- 31% in PAPS group vs 55% +/- 37% in HV group, P < .05). CONCLUSION: The CPT results obtained in this study showed that the PAPS patients studied have endothelial dysfunction.


Assuntos
Síndrome Antifosfolipídica/patologia , Endotélio Vascular/diagnóstico por imagem , Endotélio Vascular/patologia , Tomografia por Emissão de Pósitrons/métodos , Adenosina/metabolismo , Adulto , Estudos de Casos e Controles , Coagulantes/química , Circulação Coronária , Feminino , Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Estudos Prospectivos
19.
Clin Rheumatol ; 36(8): 1879-1884, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28466418

RESUMO

A consistent line of investigation proposes that fibromyalgia is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia sodium channels may play a major role in fibromyalgia pain transmission. Ambroxol is a secretolytic agent used in the treatment of various airway disorders. Recently, it was discovered that this compound is also an efficient sodium channel blocker with potent anti-neuropathic pain properties. We evaluated the add-on effect of ambroxol to the treatment of fibromyalgia. We studied 25 patients with fibromyalgia. Ambroxol was prescribed at the usual clinical dose of 30 mg PO 3 times a day × 1 month. At the beginning and at the end of the study, all participants filled out the Revised Fibromyalgia Impact Questionnaire (FIQ-R) and the 2010 ACR diagnostic criteria including the widespread pain index (WPI). At the end of the study, FIQ-R decreased from a baseline value of 62 ± 15 to 51 ± 19 (p = 0.013). Pain visual analogue scale decreased from 77 ± 14 to 56 ± 30 (p = 0.018). WPI diminished from 14.6 ± 3.1 to 10.4 ± 5.3 (p = 0.001). Side effects were minor. In this pilot study, the use of ambroxol was associated to decreased fibromyalgia pain and improved fibromyalgia symptoms. The open nature of our study does not allow extracting the placebo effect from the positive results. The drug was well tolerated. Ambroxol newly recognized pharmacological properties could theoretically interfere with fibromyalgia pain pathways. Dose escalating-controlled studies seem warranted.


Assuntos
Ambroxol/uso terapêutico , Analgésicos/uso terapêutico , Fibromialgia/tratamento farmacológico , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Medição da Dor , Projetos Piloto , Resultado do Tratamento
20.
Clin Rheumatol ; 36(12): 2813-2819, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28573372

RESUMO

This study aimed to generate a minimum list of structural and functional anatomical items about the pelvis/hip, knee, ankle/foot, gait, and lower limb innervation, which are most relevant to the practice of rheumatology. To determine their perceived relevance to clinical practice, seven members of the Mexican Clinical Anatomy Task Force compiled an initial list of 470 anatomical items. Ten local and international experts according to a 0-10 Likert scale ranked these items. Of the original list, 101 (21.48%) items were considered relevant (global rate >40). These included 36/137 (26.27%) pelvis and hip items, 25/82 (30.48%) knee items, 22/168 (13.98%) ankle/foot items, 11/68 (16.17%) neurologic items, and 7/15 (46.66%) gait-related items. We propose that these 101 anatomical items of the lower extremity, when added to the 115 anatomic items of the upper extremity and spine we previously reported, may represent an approximation to the minimal anatomical knowledge central to the competent practice of rheumatology. The meager representation of ankle and foot items may reflect a lesser emphasis in these anatomical regions during rheumatologic training. Attention to these and related items during rheumatologic training and beyond may sharpen the rheumatologist's ability in the differential diagnosis of regional pain syndromes as well as strengthen an endangered art: the rheumatologic physical examination.


Assuntos
Tornozelo/anatomia & histologia , Pé/anatomia & histologia , Marcha/fisiologia , Joelho/anatomia & histologia , Pelve/anatomia & histologia , Tornozelo/fisiologia , Fenômenos Biomecânicos/fisiologia , Pé/fisiologia , Humanos , Joelho/fisiologia , Pelve/fisiologia , Reumatologia
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