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[PMID]:28982960
[Au] Autor:Huguet I; Grossman A
[Ad] Endereço:Department of EndocrinologyHospital de la Princesa, Madrid, Spain ihm.huguet@gmail.com.
[Ti] Título:MANAGEMENT OF ENDOCRINE DISEASE: Flushing: current concepts.
[So] Source:Eur J Endocrinol;177(5):R219-R229, 2017 Nov.
[Is] ISSN:1479-683X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Flushing can be defined as a sensation of warmth accompanied by erythema that most commonly is seen on the face and which occurs in episodic attacks. Such a problem can be clinically problematic, since many conditions and drugs can be related to flushing, and while often there appears to be no underlying organic disease, it is important to exclude disorders since they may be life-threatening conditions. DESIGN AND METHODS: We performed a search in MEDLINE using the terms 'flushing' in combination with 'carcinoid syndrome', 'pheochromocytoma', 'mastocytosis', 'menopausal hot flush' and 'treatment'. European and American guidelines relating to neuroendocrine tumours, mastocytosis and menopause were reviewed. RESULTS: In this review, we discuss the main causes of flushing and propose an algorithm based on pathogenesis, which can be used to guide the clinical evaluation process. We also review recent significant developments in the assessment and treatment of the carcinoid syndrome and menopausal hot flushes, which should guide the clinical practice regarding this common but sometimes confusing condition. CONCLUSIONS: When evaluating flushing, a precise systematic approach is needed to exclude potentially serious underlying causes, although despite this, the cause of the disorder is not always found. If symptoms are not progressive, the patient should be advised about its apparently benign nature in order to avoid unnecessary studies or initiating treatments of minimal benefit.
[Mh] Termos MeSH primário: Gerenciamento Clínico
Doenças do Sistema Endócrino/diagnóstico
Doenças do Sistema Endócrino/terapia
Rubor/diagnóstico
Rubor/terapia
[Mh] Termos MeSH secundário: Neoplasias das Glândulas Suprarrenais/diagnóstico
Neoplasias das Glândulas Suprarrenais/epidemiologia
Neoplasias das Glândulas Suprarrenais/terapia
Algoritmos
Doenças do Sistema Endócrino/epidemiologia
Rubor/epidemiologia
Fogachos/diagnóstico
Fogachos/epidemiologia
Fogachos/terapia
Seres Humanos
Síndrome do Carcinoide Maligno/diagnóstico
Síndrome do Carcinoide Maligno/epidemiologia
Síndrome do Carcinoide Maligno/terapia
Menopausa/fisiologia
Tumores Neuroendócrinos/diagnóstico
Tumores Neuroendócrinos/epidemiologia
Tumores Neuroendócrinos/terapia
Feocromocitoma/diagnóstico
Feocromocitoma/epidemiologia
Feocromocitoma/terapia
Sudorese/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE
[do] DOI:10.1530/EJE-17-0295


  2 / 1179 MEDLINE  
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[PMID]:28875523
[Au] Autor:Masaoka H; Matsuo K; Sawada N; Yamaji T; Goto A; Shimazu T; Iwasaki M; Inoue M; Eto M; Tsugane S; Japan Public Health Center-based Prospective Study Group
[Ad] Endereço:Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan.
[Ti] Título:Alcohol consumption and bladder cancer risk with or without the flushing response: The Japan Public Health Center-based Prospective Study.
[So] Source:Int J Cancer;141(12):2480-2488, 2017 Dec 15.
[Is] ISSN:1097-0215
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The association between alcohol consumption and bladder cancer risk has been insufficiently investigated in East Asian populations, who frequently have the inactive enzyme for metabolizing acetaldehyde. Given that acetaldehyde associated with alcohol consumption is assessed as a carcinogen, consideration of differences in acetaldehyde exposure would aid accuracy in assessing the bladder cancer risk associated with alcohol consumption. Here, we conducted a population-based cohort study in Japan to examine this association, including information on the flushing response as a surrogate marker of the capacity of acetaldehyde metabolism. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariate Cox proportional hazard models. During follow up from 1990 through 2012 for the 95,915 subjects (45,649 men and 50,266 women, aged 40-69 years), 354 men and 110 women were newly diagnosed with bladder cancer. No significant association between alcohol consumption and bladder cancer risk was observed in the overall analysis. Among male flushers, HRs were 1.04 (95% CI 0.70-1.54), 1.67 (1.16-2.42), 1.02 (0.62-1.67) and 0.63 (0.33-1.20) for alcohol consumption of 1-150, 151-300, 301-450, >450 g/week of pure ethanol compared with non-drinkers and occasional drinkers, respectively, indicating an inverted U-shaped association between alcohol consumption and bladder cancer risk. In contrast, no significant association was identified among male non-flushers. The marginally significant interaction between alcohol consumption and the flushing response (p for interaction = 0.083) may support our hypothesis that acetaldehyde derived from alcohol consumption is associated with bladder cancer risk. A prospective study considering polymorphisms of genes involved in acetaldehyde metabolism is warranted.
[Mh] Termos MeSH primário: Consumo de Bebidas Alcoólicas/epidemiologia
Rubor/epidemiologia
Neoplasias da Bexiga Urinária/epidemiologia
[Mh] Termos MeSH secundário: Acetaldeído/metabolismo
Adulto
Idoso
Consumo de Bebidas Alcoólicas/efeitos adversos
Feminino
Rubor/metabolismo
Seres Humanos
Japão/epidemiologia
Masculino
Meia-Idade
Modelos de Riscos Proporcionais
Estudos Prospectivos
Neoplasias da Bexiga Urinária/etiologia
Neoplasias da Bexiga Urinária/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
GO1N1ZPR3B (Acetaldehyde)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE
[do] DOI:10.1002/ijc.31028


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[PMID]:28807108
[Au] Autor:Sadeghian A; Rouhana H; Oswald-Stumpf B; Boh E
[Ad] Endereço:Department of Dermatology, Tulane University, New Orleans, Louisiana.
[Ti] Título:Etiologies and management of cutaneous flushing: Malignant causes.
[So] Source:J Am Acad Dermatol;77(3):405-414, 2017 Sep.
[Is] ISSN:1097-6787
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The second article in this 2-part continuing medical education series reviews the following malignant causes of flushing: mastocytosis, medullary thyroid carcinoma, pheochromocytoma, carcinoid tumors, gastroenteropancreatic neuroendocrine tumors, bronchogenic carcinoma, vasointestinal polypeptide secreting tumors, and renal cell carcinoma. The information provided will allow physicians to better distinguish patients who have worrisome presentations that require a more thorough investigation. Appropriate diagnostic workup and treatment options for these malignancies are reviewed.
[Mh] Termos MeSH primário: Rubor/etiologia
Neoplasias/complicações
[Mh] Termos MeSH secundário: Neoplasias das Glândulas Suprarrenais/complicações
Carcinoma Neuroendócrino/complicações
Carcinoma de Células Renais/complicações
Feminino
Seres Humanos
Neoplasias Renais/complicações
Masculino
Mastocitose/complicações
Feocromocitoma/complicações
Neoplasias da Glândula Tireoide/complicações
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170816
[St] Status:MEDLINE


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[PMID]:28807107
[Au] Autor:Sadeghian A; Rouhana H; Oswald-Stumpf B; Boh E
[Ad] Endereço:Department of Dermatology, Tulane University, New Orleans, Louisiana.
[Ti] Título:Etiologies and management of cutaneous flushing: Nonmalignant causes.
[So] Source:J Am Acad Dermatol;77(3):391-402, 2017 Sep.
[Is] ISSN:1097-6787
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The flushing phenomenon may represent a physiologic or a pathologic reaction. Although flushing is usually benign, it is prudent that the physician remains aware of potentially life-threatening conditions associated with cutaneous flushing. A thorough investigation should be performed if the flushing is atypical or not clearly associated with a benign underlying process. The diagnosis often relies on a pertinent history, review of systems, physical examination, and various laboratory and imaging modalities, all of which are discussed in the 2 articles in this continuing medical education series. This article reviews flushing associated with fever, hyperthermia, emotions, menopause, medications, alcohol, food, hypersensitivity reactions, rosacea, hyperthyroidism, dumping syndrome, superior vena cava syndrome, and neurologic etiologies.
[Mh] Termos MeSH primário: Rubor/etiologia
[Mh] Termos MeSH secundário: Climatério
Feminino
Rubor/induzido quimicamente
Seres Humanos
Masculino
Avaliação de Sintomas
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170816
[St] Status:MEDLINE


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[PMID]:28353603
[Au] Autor:Zhang J; Zhang S; Song Y; Ma G; Meng Y; Ye Z; Ma X; Liu M
[Ad] Endereço:aDepartment of Medical Oncology, West China Hospital of Sichuan University, The First People's Hospital of Yibin bWest China Medical School of Sichuan University, Sichuan, PR China.
[Ti] Título:Facial flushing after alcohol consumption and the risk of cancer: A meta-analysis.
[So] Source:Medicine (Baltimore);96(13):e6506, 2017 Mar.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The association between facial flushing after alcohol consumption and the risk of cancer remains controversial. The aim of this study was to evaluate the relation between facial flushing and cancer risk. METHODS: PubMed, EMBASE, and Cochrane Library were searched for relevant literature. The patients' baseline characteristics and estimated risks were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to estimate the risk of facial flushing in cancer, and subgroup analysis was performed. RESULTS: Ten studies with 89,376 participants from East Asia were included. The pooled OR of facial flushing in all cancers was 1.43 (95% CI, 1.08-1.91), with the pooled ORs of 1.94 (95% CI, 1.33-2.83) and 0.95 (95% CI, 0.80-1.12) in men and women, respectively. The pooled ORs were also estimated in different cancer types. CONCLUSION: Our results showed that facial flushing response to alcohol was associated with higher cancer risk in men in East Asia, especially in esophageal squamous cell carcinoma, yet facial flushing was not significantly associated with cancer risk among women.
[Mh] Termos MeSH primário: Consumo de Bebidas Alcoólicas/efeitos adversos
Carcinoma de Células Escamosas/epidemiologia
Neoplasias Esofágicas/epidemiologia
Rubor/etiologia
[Mh] Termos MeSH secundário: Extremo Oriente/epidemiologia
Rubor/epidemiologia
Seres Humanos
Fatores de Risco
Fatores Sexuais
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170413
[Lr] Data última revisão:
170413
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170330
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000006506


  6 / 1179 MEDLINE  
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[PMID]:28291413
[Au] Autor:Fringeli Y; Humm AM; Ansorge A; Maestretti G
[Ad] Endereço:Spine Unit, Department of Orthopaedic Surgery; and.
[Ti] Título:Harlequin sign concomitant with Horner syndrome after anterior cervical discectomy: a case of intrusion into the cervical sympathetic system.
[So] Source:J Neurosurg Spine;26(6):684-687, 2017 Jun.
[Is] ISSN:1547-5646
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Harlequin syndrome is a rare autonomic disorder referring to the sudden development of flushing and sweating limited to one side of the face. Like Horner syndrome, associating miosis, ptosis, and anhidrosis, Harlequin syndrome is caused by disruption of the cervical sympathetic pathways. Authors of this report describe the case of a 55-year-old female who presented with both Harlequin sign and Horner syndrome immediately after anterior cervical discectomy (C6-7) with cage fusion and anterior spondylodesis. They discuss the pathophysiology underlying this striking phenomenon and the benign course of this condition. Familiarity with this unusual complication should be of particular interest for every specialist involved in cervical and thoracic surgery.
[Mh] Termos MeSH primário: Doenças do Sistema Nervoso Autônomo/etiologia
Vértebras Cervicais/cirurgia
Discotomia/efeitos adversos
Rubor/etiologia
Síndrome de Horner/etiologia
Hipo-Hidrose/etiologia
Complicações Pós-Operatórias
[Mh] Termos MeSH secundário: Doenças do Sistema Nervoso Autônomo/fisiopatologia
Feminino
Rubor/fisiopatologia
Síndrome de Horner/fisiopatologia
Seres Humanos
Hipo-Hidrose/fisiopatologia
Deslocamento do Disco Intervertebral/fisiopatologia
Deslocamento do Disco Intervertebral/cirurgia
Meia-Idade
Complicações Pós-Operatórias/fisiopatologia
Radiculopatia/fisiopatologia
Radiculopatia/cirurgia
Fusão Vertebral/efeitos adversos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.3171/2016.11.SPINE16711


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[PMID]:28282661
[Au] Autor:Dobosz L; Cwalina N; Stefaniak T
[Ad] Endereço:Department of General, Endocrine and Transplant Surgery, Gdanski Uniwersytet Medyczny, Ringgold Standard Institution, Gdansk, Poland.
[Ti] Título:Influence of Body Mass Index on Compensatory Sweating in Patients after Thoracic Sympathectomy due to Palmar Hyperhidrosis.
[So] Source:Thorac Cardiovasc Surg;65(6):497-502, 2017 Sep.
[Is] ISSN:1439-1902
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Thoracic sympathectomy (TS) is one of the most effective methods of treatment of primary hyperhidrosis. One of the side effects of this procedure is compensatory sweating (CS). The aim of our study was to evaluate the influence of body mass index (BMI) on CS in patients after TS due to palmar hyperhidrosis. Data from 157 patients with palmar hyperhidrosis who underwent TS were collected. The patients were subsequently divided in two groups according to their initial BMI: group A, BMI < 25 kg/m , and group B, BMI ≥ 25 kg/m . Objective (gravimetry) and subjective (VAS) measurements of the intensity of hyperhidrosis were taken from the patients' bodies prior to surgery, as well as 3 and 12 months after TS. Average palmar hyperhidrosis levels before the surgery did not differ significantly between the two groups (238.65 vs. 190.15; = 0.053). A statistically significant decrease in palmar hyperhidrosis was noted in both groups, both 3 and 12 months after surgery (238.65 vs. 11.86 vs. 13.5; < 0.05, and 190.15 vs. 16.67 vs. 11.81; < 0.05, respectively). The intensity of sweating over the abdomino-lumbar area differed significantly between the groups before the surgery, both in subjective (1.71 vs. 3.61; < 0.05) and objective (13.57 vs. 35.95; < 0.05) evaluations. Three months after surgical intervention, an intensification of CS was observed in both the groups; however, no statistically significant differences were observed between the two sets of patients (VAS: 4.58 vs. 5.16; = 0.38; gravimetry: 33.87 vs. 53.89; = 0.12). Twelve months after TS, CS was higher in the group with an initial BMI ≥ 25 kg/m , both in subjective and objective evaluations (3.23 vs. 4.94; = 0.03 and 18.08 vs. 80.21; = 0.026, respectively). Patients with a BMI ≥ 25 kg/m experience more severe CS after TS, both in subjective and objective evaluations.
[Mh] Termos MeSH primário: Índice de Massa Corporal
Hiperidrose/cirurgia
Obesidade/complicações
Complicações Pós-Operatórias/etiologia
Glândulas Sudoríparas/inervação
Sudorese
Simpatectomia/efeitos adversos
Nervos Torácicos/cirurgia
[Mh] Termos MeSH secundário: Adulto
Feminino
Rubor
Mãos
Seres Humanos
Hiperidrose/diagnóstico
Hiperidrose/fisiopatologia
Masculino
Obesidade/diagnóstico
Complicações Pós-Operatórias/fisiopatologia
Fatores de Risco
Índice de Gravidade de Doença
Simpatectomia/métodos
Nervos Torácicos/fisiopatologia
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE
[do] DOI:10.1055/s-0037-1599797


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[PMID]:28267211
[Au] Autor:Shi DD; Yuppa DP; Dutton T; Brais LK; Minden SL; Braun IM; Kulke MH; Chan JA; Meyer FL
[Ad] Endereço:Harvard Medical School, Boston, Massachusetts.
[Ti] Título:Retrospective review of serotonergic medication tolerability in patients with neuroendocrine tumors with biochemically proven carcinoid syndrome.
[So] Source:Cancer;123(14):2735-2742, 2017 Jul 15.
[Is] ISSN:1097-0142
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Patients with carcinoid tumors frequently could benefit from the pharmacologic treatment of depression and anxiety. However, many prescribers avoid serotonergic medications due to the theoretical risk of exacerbating carcinoid syndrome. METHODS: The authors conducted a retrospective chart review of patients with carcinoid tumors and elevated serotonin levels (as measured by 24-hour urine 5-hydroxyindoleacetic acid [5-HIAA]) at Dana-Farber/Brigham and Women's Cancer Center who initiated treatment with serotonergic antidepressants after a carcinoid diagnosis from 2003 to 2016. Each medication regimen was categorized based on the presence of adverse interactions as defined by clinical worsening of symptoms of carcinoid syndrome in the absence of progressive disease that temporally correlated with a serotonergic medication trial. RESULTS: A total of 73 serotonergic regimens received by 52 patients were included in the primary analysis. Among these medication trials, 8.2% of the regimens (6 regimens) were categorized as being associated with a likely adverse interaction, 61.6% of the regimens (45 regimens) were categorized as having no adverse reaction, 9.6% of the regimens (7 regimens) were categorized as an unlikely adverse reaction, and 20.6% of the regimens (15 regimens) were categorized as unknown. It is interesting to note that none of the 73 trials resulted in a carcinoid crisis requiring emergency care or hospitalization. Only 3 patients discontinued serotonergic medications due to worsening carcinoid syndrome. CONCLUSIONS: Serotonergic medications appear to be a safe option for the treatment of depressive and anxiety symptoms in the majority of patients with neuroendocrine tumors and carcinoid syndrome. In the current study, <10% of patients developed a combination of flushing, diarrhea, and bloating after the initiation of serotonergic medications. Clinicians can begin with low doses, monitor these symptoms, and reduce the dose or discontinue the medication if necessary. Cancer 2017;123:2735-42. © 2017 American Cancer Society.
[Mh] Termos MeSH primário: Ansiedade/tratamento farmacológico
Depressão/tratamento farmacológico
Síndrome do Carcinoide Maligno/metabolismo
Inibidores da Captação de Serotonina/uso terapêutico
[Mh] Termos MeSH secundário: Ansiedade/complicações
Tumor Carcinoide/complicações
Tumor Carcinoide/metabolismo
Depressão/complicações
Diarreia/induzido quimicamente
Diarreia/etiologia
Feminino
Rubor/induzido quimicamente
Rubor/etiologia
Seres Humanos
Ácido Hidroxi-Indolacético/urina
Masculino
Síndrome do Carcinoide Maligno/complicações
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Serotonin Uptake Inhibitors); 54-16-0 (Hydroxyindoleacetic Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170308
[St] Status:MEDLINE
[do] DOI:10.1002/cncr.30633


  9 / 1179 MEDLINE  
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[PMID]:28189131
[Au] Autor:Lau F; Gardiner M
[Ti] Título:Oxycodone/naloxone: An unusual adverse drug reaction.
[So] Source:Aust Fam Physician;46(1):42-43, 2017 Jan/Feb.
[Is] ISSN:0300-8495
[Cp] País de publicação:Australia
[La] Idioma:eng
[Mh] Termos MeSH primário: Diazepam/administração & dosagem
Naloxona/efeitos adversos
Oxicodona/efeitos adversos
Síndrome de Abstinência a Substâncias/diagnóstico
[Mh] Termos MeSH secundário: Analgésicos Opioides/administração & dosagem
Analgésicos Opioides/efeitos adversos
Analgésicos Opioides/uso terapêutico
Ansiolíticos/administração & dosagem
Ansiolíticos/uso terapêutico
Diazepam/uso terapêutico
Combinação de Medicamentos
Quimioterapia Combinada
Doença Hepática Terminal
Varizes Esofágicas e Gástricas
Feminino
Rubor/etiologia
Seres Humanos
Meia-Idade
Mioclonia/etiologia
Naloxona/administração & dosagem
Naloxona/uso terapêutico
Oxicodona/administração & dosagem
Oxicodona/uso terapêutico
Derivação Portossistêmica Transjugular Intra-Hepática
Agitação Psicomotora/etiologia
Inibidores da Captação de Serotonina/uso terapêutico
Síndrome de Abstinência a Substâncias/tratamento farmacológico
Síndrome de Abstinência a Substâncias/fisiopatologia
Taquicardia/etiologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Anti-Anxiety Agents); 0 (Drug Combinations); 0 (Serotonin Uptake Inhibitors); 0 (oxycodone naloxone combination); 36B82AMQ7N (Naloxone); CD35PMG570 (Oxycodone); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170213
[St] Status:MEDLINE


  10 / 1179 MEDLINE  
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[PMID]:28119443
[Au] Autor:Dunbar RL; Goel H; Tuteja S; Song WL; Nathanson G; Babar Z; Lalic D; Gelfand JM; Rader DJ; Grove GL
[Ad] Endereço:University of Pennsylvania Institute for Translational Medicine and Therapeutics, Philadelphia PA richard.dunbar@uphs.upenn.edu.
[Ti] Título:Measuring niacin-associated skin toxicity (NASTy) stigmata along with symptoms to aid development of niacin mimetics.
[So] Source:J Lipid Res;58(4):783-797, 2017 Apr.
[Is] ISSN:1539-7262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Though cardioprotective, niacin monotherapy is limited by unpleasant cutaneous symptoms mimicking dermatitis: niacin-associated skin toxicity (NASTy). Niacin is prototypical of several emerging drugs suffering off-target rubefacient properties whereby agonizing the GPR109A receptor on cutaneous immune cells provokes vasodilation, prompting skin plethora and , as well as , , and , and systemically, heat loss, , chills, and rigors. Typically, NASTy effects are described by subjective patient-reported perception, at best semi-quantitative and bias-prone. Conversely, objective, quantitative, and unbiased methods measuring NASTy stigmata would facilitate research to abolish them, motivating development of several objective methods. In early drug development, such methods might better predict clinical tolerability in larger clinical trials. Measuring cutaneous stigmata may also aid investigations of vasospastic, ischemic, and inflammatory skin conditions. We present methods to measure NASTy physical stigmata to facilitate research into novel niacin mimetics/analogs, detailing characteristics of each technique following niacin, and how NASTy stigmata relate to symptom perception. We gave niacin orally and measured by colorimetry and white-light spectroscopy, plethora by laser Doppler flowmetry, and / by thermometry. Surprisingly, each stigma's abruptness predicted symptom perception, whereas peak intensity did not. These methods are adaptable to study other rubefacient drugs or dermatologic and vascular disorders.
[Mh] Termos MeSH primário: Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia
Hipolipemiantes/efeitos adversos
Irritantes/efeitos adversos
Niacina/efeitos adversos
Pele/fisiopatologia
[Mh] Termos MeSH secundário: Biomimética
Colorimetria
Relação Dose-Resposta a Droga
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação
Dislipidemias/complicações
Dislipidemias/tratamento farmacológico
Rubor/induzido quimicamente
Rubor/patologia
Seres Humanos
Hipolipemiantes/química
Hipolipemiantes/uso terapêutico
Irritantes/química
Irritantes/uso terapêutico
Fluxometria por Laser-Doppler
Niacina/química
Niacina/uso terapêutico
Receptores Acoplados a Proteínas-G/agonistas
Receptores Acoplados a Proteínas-G/metabolismo
Receptores Nicotínicos/metabolismo
Pele/efeitos dos fármacos
Vasodilatação/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HCAR2 protein, human); 0 (Hypolipidemic Agents); 0 (Irritants); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Nicotinic); 2679MF687A (Niacin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE
[do] DOI:10.1194/jlr.D071696



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