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1.
Eur J Neurol ; 27(3): 536-541, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31574197

RESUMO

BACKGROUND AND PURPOSE: Although migraine is the second most disabling condition worldwide, there is poor awareness of it. The objective was to assess the awareness of migraine and previous diagnostic and therapeutic consultations and treatments in a large international population of migraineurs. METHODS: This was a multicentre study conducted in 12 headache centres in seven countries. Each centre recruited up to 100 patients referred for a first visit and diagnosed with migraine. Subjects were given a structured clinical questionnaire-based interview about the perceptions of the type of headache they suffered from, its cause, previous diagnoses, investigations and treatments. RESULTS: In all, 1161 patients completed the study. Twenty-eight per cent of participants were aware that they suffered from migraine. Sixty-four per cent called their migraine 'headache'; less commonly they used terms such as 'cervical pain' (4%), tension headache (3%) and sinusitis (1%). Eight per cent of general practitioners and 35% of specialists (of whom 51% were neurologists and/or headache specialists) consulted for migraine formulated the correct diagnosis. Before participating in the study, 50% of patients had undergone X-ray, computed tomography and/or magnetic resonance imaging of the cervical spine and 76% underwent brain and/or cervical spine imaging for migraine. Twenty-eight per cent of patients had received symptomatic migraine-specific medications and 29% at least one migraine preventive medication. CONCLUSIONS: Although migraine is a very common disease, poor awareness of it amongst patients and physicians is still an issue in several countries. This highlights the importance of the promotion of migraine awareness to reduce its burden and limit direct and indirect costs and the risk of exposure to useless investigations.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/psicologia , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Estudos de Coortes , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Cefaleia/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/terapia , Médicos , Inquéritos e Questionários , Tomografia Computadorizada por Raios X , Adulto Jovem
2.
Neurol Sci ; 40(7): 1425-1431, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30941628

RESUMO

To improve patient care and help clinical research, the Neuropathic Pain Special Interest Group of the Italian Neurological Society appointed a task force to elaborate a consensus statement on pharmacoresistant neuropathic pain. The task force included 19 experts in neuropathic pain. These experts participated in a Delphi survey consisting of three consecutive rounds of questions and a face-to-face meeting, designed to achieve a consensus definition of pharmacoresistant neuropathic pain. In the three rounds of questions, the participants identified and described the main distinguishing features of pharmacoresistance. In the face-to-face meeting the participants discussed the clinical features determining pharmacoresistance. They finally agreed that neuropathic pain is pharmacoresistant when "the patient does not reach the 50% reduction of pain or an improvement of at least 2 points in the Patient Global Impression of Change, having used all drug classes indicated as first, second, or third line in the most recent and widely agreed international guidelines, for at least 1 month after titration to the highest tolerable dose." Our consensus statement might be useful for identifying eligible patients for invasive treatments, and selecting patients in pharmacological trials, thus improving patient care and helping clinical research.


Assuntos
Neuralgia/classificação , Dor Intratável/classificação , Técnica Delphi , Resistência a Medicamentos , Humanos , Neuralgia/diagnóstico , Neuralgia/terapia , Dor Intratável/diagnóstico , Dor Intratável/terapia
3.
Pharmacogenomics J ; 12(2): 96-104, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21221126

RESUMO

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe, potentially life threatening adverse drug reactions characterized by skin blistering. Previous studies have identified drug-specific and population-specific genetic risk factors with large effects. In this study, we report the first genome-wide association study (GWAS) of SJS/TEN induced by a variety of drugs. Our aim was to identify common genetic risk factors with large effects on SJS/TEN risk. We conducted a genome-wide analysis of 96 retrospective cases and 198 controls with a panel of over one million single-nucleotide polymorphisms (SNPs). We further improved power with about 4000 additional controls from publicly available datasets. No genome-wide significant associations with SNPs or copy number variants were observed, although several genomic regions were suggested that may have a role in predisposing to drug-induced SJS/TEN. Our GWAS did not find common, highly penetrant genetic risk factors responsible for SJS/TEN events in the cases selected.


Assuntos
Estudo de Associação Genômica Ampla , Síndrome de Stevens-Johnson/induzido quimicamente , Síndrome de Stevens-Johnson/etiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Análise de Componente Principal , Estudos Retrospectivos , Síndrome de Stevens-Johnson/genética
4.
Eur Respir J ; 37(4): 823-34, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20693251

RESUMO

The mechanism(s) involved in the development of pulmonary hypertension (PH) in COPD is still the object of investigation. Cigarette smoke (CS) may lead to remodelling of intrapulmonary vessels and dynamic changes in vascular function, at least in some smokers. A role for proteases in PH has been recently put forward. We investigated, in smoking mice, the role of protease-activated receptor (PAR)-2 in the pathogenesis of PH associated with emphysema. We demonstrated that CS exposure can modulate PAR-2 expression in mouse lung. Acute CS exposure induces in wildtype (WT) and in transgenic mice over-expressing PAR-2 (FVB(PAR-2-TgN)) a similar degree of neutrophil influx in bronchoalveolar lavage fluids. After chronic CS exposure WT and FVB(PAR-2-TgN) mice show emphysema, but only transgenic mice develop muscularisation of small intrapulmonary vessels that precedes the development of PH (~45% increase) and right ventricular hypertrophy. Smoking in FVB(PAR-2-TgN) mice results in an imbalance between vasoconstrictors (especially endothelin-1) and vasodilators (i.e. vascular endothelial growth factor, endothelial nitric oxide synthase and inducible nitric oxide synthase) and enhanced production of growth factors involved both in fibroblast-smooth muscle cell transaction (i.e. platelet-derived growth factor (PDGF) and transforming growth factor ß) and vascular cell proliferation (PDGF). PAR-2 signalling can influence the production and release of many factors, which may play a role in the development of PH in smokers.


Assuntos
Hipertensão Pulmonar/etiologia , Receptor PAR-2/biossíntese , Fumar/efeitos adversos , Animais , Apoptose , Líquido da Lavagem Broncoalveolar , Proliferação de Células , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hipertensão Pulmonar/metabolismo , Hipertrofia Ventricular Direita , Imuno-Histoquímica/métodos , Pulmão/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , RNA/metabolismo , Transdução de Sinais
5.
Nat Med ; 3(8): 904-7, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9256283

RESUMO

Plasma extravasation from postcapillary venules is one of the earliest steps of inflammation. Substance P (SP) and bradykinin (BK) mediate extravasation and cause hypotension. The cell-surface enzyme neutral endopeptidase (NEP) inactivates both peptides. Thus, absence of NEP may predispose development of inflammation and hypotension. We examined these possibilities in mice in which the NEP gene was deleted by homologous recombination. There was widespread basal plasma extravasation in postcapillary venular endothelia in NEP-/- mice, which was reversed by recombinant NEP and antagonists of SP (NK1) and BK (B2) receptors. Mean arterial blood pressure was 20% lower in NEP-/- animals, but this was unaffected by reintroduction of recombinant NEP and the kinin receptor antagonists. The hypotension was also independent of nitric oxide (NO), because NEP-/- mice treated with a NO synthase inhibitor remained hypotensive relative to the wild type. Thus, NEP has important roles in regulating basal microvascular permeability by degrading SP and BK, and may regulate blood pressure set point through a mechanism that is independent of SP, BK and NO. The use of NEP antagonists as candidate drugs in cardiovascular disease is suggested by the blood pressure data reported herein.


Assuntos
Pressão Sanguínea/fisiologia , Capilares/fisiologia , Permeabilidade Capilar/fisiologia , Neprilisina/fisiologia , Vênulas/fisiologia , Animais , Bradicinina/fisiologia , Antagonistas dos Receptores da Bradicinina , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neprilisina/genética , Antagonistas dos Receptores de Neurocinina-1 , Substância P/fisiologia
6.
Nat Med ; 6(2): 151-8, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10655102

RESUMO

Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 and, by unknown mechanisms, induce widespread inflammation. We found that a large proportion of primary spinal afferent neurons, which express proteinase-activated receptor 2, also contain the proinflammatory neuropeptides calcitonin gene-related peptide and substance P. Trypsin and tryptase directly signal to neurons to stimulate release of these neuropeptides, which mediate inflammatory edema induced by agonists of proteinase-activated receptor 2. This new mechanism of protease-induced neurogenic inflammation may contribute to the proinflammatory effects of mast cells in human disease. Thus, tryptase inhibitors and antagonists of proteinase-activated receptor 2 may be useful anti-inflammatory agents.


Assuntos
Inflamação/etiologia , Receptores de Trombina/agonistas , Animais , Sequência de Bases , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Quimases , Sondas de DNA , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Humanos , Hibridização In Situ , Masculino , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Receptor PAR-2 , Receptores de Trombina/metabolismo , Serina Endopeptidases/metabolismo , Transdução de Sinais , Substância P/metabolismo , Tripsina/metabolismo , Triptases
7.
J Pharmacol Exp Ther ; 335(3): 622-35, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20805306

RESUMO

The novel quaternary ammonium salt (3R)-3-[[[(3-fluorophenyl)[(3,4,5-trifluorophenyl)methyl]amino]carbonyl]oxy]-1-[2-oxo-2-(2-thienyl)ethyl]-1-azoniabicyclo[2.2.2]octane bromide (CHF5407) showed subnanomolar affinities for human muscarinic M1 (hM1), M2 (hM2), and M3 (hM3) receptors and dissociated very slowly from hM3 receptors (t(½) = 166 min) with a large part of the receptorial complex (54%) remaining undissociated at 32 h from radioligand washout. In contrast, [(3)H]CHF5407 dissociated quickly from hM2 receptors (t(½) = 31 min), whereas [(3)H]tiotropium dissociated slowly from both hM3 (t(½) = 163 min) and hM2 receptor (t(½) = 297 min). In the guinea pig isolated trachea and human isolated bronchus, CHF5407 produced a potent (pIC(50) = 9.0-9.6) and long-lasting (up to 24 h) inhibition of M3 receptor-mediated contractile responses to carbachol. In the guinea pig electrically driven left atrium, the M2 receptor-mediated inhibitory response to carbachol was recovered more quickly in CHF5407-pretreated than in tiotropium-pretreated preparations. CHF5407, administered intratracheally to anesthetized guinea pigs, potently inhibited acetylcholine (Ach)-induced bronchoconstriction with an ED(50) value of 0.15 nmol/kg. The effect was sustained over a period of 24 h, with a residual 57% inhibition 48 h after antagonist administration at 1 nmol/kg. In conscious guinea pigs, inhaled CHF5407 inhibited Ach-induced bronchoconstriction for at least 24 h as did tiotropium at similar dosages. Cardiovascular parameters in anesthetized guinea pigs were not significantly changed by CHF5407, up to 100 nmol/kg i.v. and up to 1000 nmol/kg i.t. In conclusion, CHF5407 shows a prolonged antibronchospastic activity both in vitro and in vivo, caused by a very slow dissociation from M3 receptors. In contrast, CHF5407 is markedly short-acting at M2 receptors, a behavior not shared by tiotropium.


Assuntos
Broncoconstrição/efeitos dos fármacos , Broncodilatadores/farmacologia , Carbamatos/farmacologia , Antagonistas Muscarínicos/farmacologia , Quinuclidinas/farmacologia , Receptor Muscarínico M3/antagonistas & inibidores , Acetilcolina/farmacologia , Idoso , Anestesia , Animais , Pressão Sanguínea/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Espasmo Brônquico/induzido quimicamente , Espasmo Brônquico/tratamento farmacológico , Espasmo Brônquico/prevenção & controle , Broncoconstritores/farmacologia , Broncodilatadores/administração & dosagem , Broncodilatadores/metabolismo , Células CHO , Carbacol/farmacologia , Carbamatos/administração & dosagem , Carbamatos/metabolismo , Cricetinae , Cricetulus , Diaminas/administração & dosagem , Diaminas/farmacologia , Cobaias , Átrios do Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/metabolismo , Contração Miocárdica/efeitos dos fármacos , Quinuclidinas/administração & dosagem , Quinuclidinas/metabolismo , Receptor Muscarínico M1/genética , Receptor Muscarínico M1/metabolismo , Receptor Muscarínico M2/agonistas , Receptor Muscarínico M2/antagonistas & inibidores , Receptor Muscarínico M2/genética , Receptor Muscarínico M2/metabolismo , Receptor Muscarínico M3/agonistas , Receptor Muscarínico M3/genética , Receptor Muscarínico M3/metabolismo , Derivados da Escopolamina/administração & dosagem , Derivados da Escopolamina/metabolismo , Derivados da Escopolamina/farmacologia , Brometo de Tiotrópio , Traqueia/efeitos dos fármacos , Transfecção , Função Ventricular Esquerda/efeitos dos fármacos
8.
Cephalalgia ; 30(6): 744-6, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19732077

RESUMO

Umbellularia californica, a shrub or tree indigenous to southwestern Oregon and northern California, is commonly known as headache tree, probably because it is reported that its scent can cause headache. Here, we report the case of a 69-year-old Italian gardener, affected during his young adult age by cluster headache, who, 10 years from his last cluster episode, developed shorter-lasting cluster-like headache attacks after and at any time he was exposed to U. californica scent. The present case indicates that, even though endogenous mechanisms causing the cluster headache were no longer present, susceptibility to exogenous triggers remains active in this patient, and suggests that identification of the constituent(s) of U. californica responsible for triggering cluster headache-like attacks may help in the understanding of the hitherto elusive mechanism of cluster headache.


Assuntos
Cefaleia Histamínica/etiologia , Odorantes , Umbellularia/efeitos adversos , Idoso , Humanos , Masculino , Adulto Jovem
9.
Pharmacoepidemiol Drug Saf ; 19(9): 954-60, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20623521

RESUMO

PURPOSE: Mostly because of comorbidity and drugs consumption, older persons are often exposed to an increased risk of sub-optimal prescribing (SP). At present, few studies investigated the association between SP and long-term health outcomes. We examined the relation between SP and the risk of mortality and hospitalization in Italian older community-dwellers. METHODS: Older (65+ years) community-dwelling residents of a small town in Tuscany were enrolled in a longitudinal study. SP was defined as polypharmacy (use of 5+ drugs), prescription of inappropriate drugs (ID) according to Beers' criteria, and of potentially interacting drugs (PID), evaluated in 1995 and 1999. These three forms of SP were entered as time-dependent exposures into multivariable Cox regression analysis models, whose outcomes were mortality and hospitalizations through 2003. RESULTS: Of 1022 participants (mean age 73.0 +/- 6.8, 57% women), 220 were evaluated in 1995, 234 in 1999 and 568 in both waves. In univariate analysis, mortality was two-fold higher in participants with polypharmacy (73.4/1000 person/years, 95% CI 58.2-92.4 vs. 34.1, 95% CI 29.7-39.2; p < 0.001) or PID (72.7/1000 person/years, 95% CI 46.3-113.9 vs. 38.0, 95% CI 33.5-43.1; p < 0.001), whereas it was unrelated to the presence of ID. Hospitalization rates were independent of any form of SP. In multivariable models, polypharmacy, ID, and PID were no longer associated with an increased risk of death, and ID predicted a slightly increased risk of hospitalizations (HR 1.03, 95% CI 1.0-1.06, p = 0.048). CONCLUSIONS: In this cohort, SP was not associated with an excess risk of poor health outcomes.


Assuntos
Avaliação de Resultados em Cuidados de Saúde , Polimedicação , Padrões de Prática Médica/normas , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Interações Medicamentosas , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Itália , Estudos Longitudinais , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo
10.
Methods Find Exp Clin Pharmacol ; 32(1): 39-45, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20383345

RESUMO

The purpose of this study was to compare the efficacy of a 14-day course of prulifloxacin 600 mg with standard antibiotic therapy for the treatment of chronic prostatitis due to Chlamydia trachomatis (Ct) infection. All patients with clinical and instrumental diagnosis of bacterial chronic prostatitis (CP) due to Ct infection were enrolled. After randomization, all patients were administered oral prulifloxacin 600 mg once daily for 14 days or doxycycline 100 mg orally twice daily for 21 days. At enrollment and 30 days after beginning treatment, all patients underwent microbiological cultures for uropathogens bacteria and yeasts, DNA extraction and mucosal IgA evaluation for Ct diagnosis, seminal plasma IL-8 evaluation and serum IgA and IgG anti-Ct analysis. The National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) was given to each patient. A total of 109 patients received prulifloxacin and 102 received standard therapy. Prulifloxacin had clinical efficacy rates equivalent to standard therapy (82.5% vs. 79.9%) (P = 0.08) and showed superior microbiological efficacy rates compared to standard therapy, in terms of decreasing mucosal IgA (P < 0.001) and IL-8 levels (P < 0.001). Prulifloxacin was also equivalent to standard therapy for clinical success, as demonstrated by a decrease in the number of patients affected by CP due to Ct infection.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Chlamydia/tratamento farmacológico , Dioxolanos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Piperazinas/uso terapêutico , Prostatite/tratamento farmacológico , Administração Oral , Adulto , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/efeitos dos fármacos , Chlamydia trachomatis/isolamento & purificação , Doxiciclina/uso terapêutico , Seguimentos , Humanos , Imunoglobulina A/efeitos dos fármacos , Imunoglobulina A/metabolismo , Interleucina-8/efeitos dos fármacos , Interleucina-8/metabolismo , Masculino , Estudos Prospectivos , Prostatite/microbiologia , Resultado do Tratamento
11.
Handb Exp Pharmacol ; (187): 49-61, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18825335

RESUMO

The transient receptor potential (TRP) family of channels is represented by at least six members in primary sensory neurons. These include the TRP vanilloid subtypes 1 (TRPV1), 2, 3, and 4, the cold and menthol receptor TRPM8, and TRPA1. Much interest has been directed to the study of the TRPV1, because capsaicin has been instrumental in discovering the unique role of a subset of primary sensory neurons in causing nociceptive responses, in activating reflex pathways including cough, and in producing neurogenic inflammation. TRPV1 is now regarded as an integrator of diverse sensory modalities because it undergoes marked plasticity and sensitization through a variety of mechanisms, including activation of G-protein-coupled or tyrosine kinase receptors. Evidence in experimental animals and in patients with airway diseases indicates a marked hypersensitivity to cough induced by TRPV1 agonists. Recent studies with newly developed high-affinity and selective TRPV1 antagonists have revealed that TRPV1 inhibition reduces cough induced by citric acid or antigen challenge.


Assuntos
Tosse/fisiopatologia , Canais de Potencial de Receptor Transitório/fisiologia , Animais , Tosse/patologia , Humanos , Neurite (Inflamação)/patologia , Neurite (Inflamação)/fisiopatologia , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/fisiologia
12.
Gut ; 57(5): 628-33, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18182589

RESUMO

BACKGROUND AND AIMS: It has recently been described that bradykinin B(2) receptors are expressed in the human gallbladder and that their activation induces a powerful contraction, especially in acute cholecystitis tissues. Here the role of the B(1) receptor in the contractility of control and inflamed human gallbladder was investigated. METHODS: Strips of human gallbladder from either acute gallstone cholecystitis or elective gastro-entero-pancreatic surgery (control) were assessed in vitro and processed for reverse transcription-PCR analysis. Cumulative concentration-response curves with the selective B(1) receptor agonist, Lys-Des-Arg(9)-bradykinin, cholecystokinin and carbachol were performed in control and cholecystitis specimens. RESULTS: Lys-Des-Arg(9)-bradykinin concentration-dependently contracted strips of control gallbladders and its motor effect was higher in inflamed gallbladders. Lys-Des-Arg(9)-bradykinin-induced contraction was not altered by pretreatment with the selective bradykinin B(2) receptor antagonist, HOE140 (1 microM), the NK(1) (SR140333), NK(2) (SR48968) and NK(3) (SR142801) tachykinin receptor antagonists (all 1 microM), the muscarinic acetylcholine receptor antagonist, atropine (1 microM), and the cyclo-oxygenase inhibitor, indomethacin (5 microM). In contrast, the Lys-Des-Arg(9)-bradykinin-induced motor response was significantly reduced by the selective B(1) receptor antagonist, R-715. Finally, quantitative real-time PCR analysis indicated that B(1) receptor mRNA levels were significantly higher in cholecystitis smooth muscle specimens, when compared with that observed in control tissues. CONCLUSIONS: Bradykinin B(1) receptor has an important role as a spasmogen of human gallbladder, and selective antagonists of the B(1) receptor may represent a valid therapeutic option to control pain in patients with acute cholecystitis.


Assuntos
Antagonistas de Receptor B1 da Bradicinina , Antagonistas de Receptor B2 da Bradicinina , Colecistite/tratamento farmacológico , Vesícula Biliar/efeitos dos fármacos , Adulto , Idoso , Atropina/farmacologia , Colecistite/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Feminino , Vesícula Biliar/fisiologia , Humanos , Indometacina/farmacologia , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/farmacologia , Receptor B1 da Bradicinina/metabolismo , Receptor B2 da Bradicinina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
J Affect Disord ; 249: 226-233, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30776664

RESUMO

BACKGROUND: The Mental Pain Questionnaire (MPQ) is a self-report questionnaire developed to assess mental pain. The aim of the present study was to test the clinimetric properties of the MPQ. METHODS: A sample of 200 migraine outpatients were enrolled; homogeneity of MPQ was assessed by Mokken Analysis; item-level severity and item-level sensitivity were calculated via Two-Parameter Logistic model; Total Information Function was evaluated to assess reliability of MPQ; internal consistency was calculated via Cronbach's alpha and Sijtsma and Molenaar rho; sensitivity and specificity were assessed via Receiver Operating Characteristic curves. RESULTS: The MPQ showed unidimensional factor structure; satisfactory homogeneity of the item and total score, except items 4 ("my pain is everywhere") and 6 ("I cannot understand why I feel this pain"); good discrimination, except item 7 ("I feel empty"); low information provided by items 4, 6, 7; good reliability for mild and high levels of mental pain; poor reliability for low levels of mental pain; acceptable internal consistency; acceptable sensitivity and specificity. LIMITATIONS: The sample size is barely sufficient to calculate item parameters; it is a monocentric study that enrolled outpatients from a tertiary facility; the study enrolled migraine outpatients not affected by other medical disease. CONCLUSIONS: The MPQ showed good psychometric properties. Items 4, 6, 7 should be considered with caution when migraine patients are evaluated. A score of at least 3 indicates mental pain clinically relevant, a score of at least 2 indicates distress. These data are preliminary and refer to migraine patients, results might be different in psychiatric populations.


Assuntos
Transtornos de Enxaqueca/diagnóstico , Medição da Dor/normas , Dor/psicologia , Inquéritos e Questionários/normas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Medidas de Resultados Relatados pelo Paciente , Psicometria , Reprodutibilidade dos Testes , Autorrelato , Sensibilidade e Especificidade
14.
Cephalalgia ; 28(1): 9-17, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17888011

RESUMO

Ethanol stimulating transient receptor potential vanilloid 1 (TRPV1) on primary sensory neurons promotes neurogenic inflammation, including calcitonin gene-related peptide (CGRP)-mediated coronary dilation. Alcoholic beverages trigger migraine attacks and activation of trigeminal neurons plays a role in migraine. We have investigated in guinea pigs whether ethanol by TRPV1 stimulation causes neurogenic inflammation in the trigeminovascular system. Ethanol-evoked release of neuropeptides from slices of dura mater was abolished by Ca(2+) removal, capsaicin pretreatment and the TRPV1 antagonist, capsazepine. Intragastric ethanol increased plasma extravasation in dura mater, an effect abolished by capsazepine and the NK1 receptor antagonist, SR140333, and caused vasodilation around the middle meningeal artery, an effect abolished by capsazepine and the CGRP receptor antagonist, BIBN4096BS. Vasodilation of meningeal vessels by TRPV1 activation and CGRP release may be relevant to the mechanism by which alcohol ingestion triggers migraine attacks.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Etanol/farmacologia , Canais de Cátion TRPV/metabolismo , Gânglio Trigeminal/irrigação sanguínea , Gânglio Trigeminal/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Animais , Dura-Máter/irrigação sanguínea , Dura-Máter/efeitos dos fármacos , Dura-Máter/metabolismo , Cobaias , Masculino , Canais de Cátion TRPV/fisiologia , Gânglio Trigeminal/metabolismo , Vasodilatação/fisiologia , Vasodilatadores/farmacologia
15.
Nat Neurosci ; 5(6): 546-51, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11992116

RESUMO

The vanilloid receptor-1 (VR1) is a heat-gated ion channel that is responsible for the burning sensation elicited by capsaicin. A similar sensation is reported by patients with esophagitis when they consume alcoholic beverages or are administered alcohol by injection as a medical treatment. We report here that ethanol activates primary sensory neurons, resulting in neuropeptide release or plasma extravasation in the esophagus, spinal cord or skin. Sensory neurons from trigeminal or dorsal root ganglia as well as VR1-expressing HEK293 cells responded to ethanol in a concentration-dependent and capsazepine-sensitive fashion. Ethanol potentiated the response of VR1 to capsaicin, protons and heat and lowered the threshold for heat activation of VR1 from approximately 42 degrees C to approximately 34 degrees C. This provides a likely mechanistic explanation for the ethanol-induced sensory responses that occur at body temperature and for the sensitivity of inflamed tissues to ethanol, such as might be found in esophagitis, neuralgia or wounds.


Assuntos
Capsaicina/análogos & derivados , Etanol/farmacologia , Nociceptores/efeitos dos fármacos , Nociceptores/fisiologia , Receptores de Droga/fisiologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capsaicina/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Etanol/administração & dosagem , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Temperatura Alta , Humanos , Masculino , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/fisiologia , Concentração Osmolar , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/metabolismo , Limiar Sensorial/efeitos dos fármacos , Substância P/metabolismo , Canais de Cátion TRPV , Termorreceptores/efeitos dos fármacos , Termorreceptores/fisiologia , Gânglio Trigeminal/citologia , Gânglio Trigeminal/efeitos dos fármacos
16.
J Clin Invest ; 94(5): 2036-44, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7525653

RESUMO

We evaluated the effects of nitric oxide (NO) generators and endogenous production of NO elicited by substance P (SP) in the angiogenesis process. Angiogenesis was monitored in the rabbit cornea in vivo and in vitro by measuring the growth and migration of endothelial cells isolated from coronary postcapillary venules. The angiogenesis promoted in the rabbit cornea by [Sar9]-SP-sulfone, a stable and selective agonist for the tachykinin NK1 receptor, and by prostaglandin E1 (PGE1), was potentiated by sodium nitroprusside (SNP). Conversely, the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), given systemically, inhibited angiogenesis elicited by [Sar9]-SP-sulfone and by PGE1. Endothelial cells exposed to SNP exhibited an increase in thymidine incorporation and in total cell number. Exposure of the cells to NO generating drugs, such as SNP, isosorbide dinitrate, and glyceryl trinitrate, produced a dose-dependent increase in endothelial cell migration. Capillary endothelial cell proliferation and migration produced by SP were abolished by pretreatment with the NO synthase inhibitors N omega-mono-methyl-L-arginine (L-NMMA), N omega-nitro-L-arginine (L-NNA), and L-NAME. Exposure of the cells to SP activated the calcium-dependent NO synthase. Angiogenesis and endothelial cell growth and migration induced by basic fibroblast growth factor were not affected by NO synthase inhibitors. These data indicate that NO production induced by vasoactive agents, such as SP, functions as an autocrine regulator of the microvascular events necessary for neovascularization and mediates angiogenesis.


Assuntos
Endotélio Vascular/citologia , Neovascularização Patológica/etiologia , Óxido Nítrico/fisiologia , Substância P/farmacologia , Aminoácido Oxirredutases/antagonistas & inibidores , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Divisão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , GMP Cíclico/biossíntese , GMP Cíclico/sangue , DNA/biossíntese , Endotélio Vascular/efeitos dos fármacos , NG-Nitroarginina Metil Éster , Óxido Nítrico Sintase , Nitroprussiato/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Coelhos
17.
Clin Exp Allergy ; 37(12): 1788-97, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17941913

RESUMO

BACKGROUND: An induction of reactive oxygen species (ROS) is characteristic for inflammation but the exact pathways have not been identified for allergic airway diseases so far. OBJECTIVE: The aim of this study was to characterize the role of the tachykinin NK-1 receptor on ROS production during allergen challenge and subsequent inflammation and remodelling. METHODS: Precision-cut lung slices of ovalbumin (OVA)-sensitized mice were cultivated and ROS-generation in response to OVA challenge (10 microg/mL) was examined by the 2',7'-dichloroflourescein-diacetate method. Long-term ROS effects on epithelial proliferation were investigated by 5-bromo-2'-deoxyuridine incorporation (72 h). In vivo, the results were validated in OVA-sensitized animals which were treated intra-nasally with either placebo, the tachykinin neurokinin 1 (NK-1) receptor antagonist SR 140333 or the anti-oxidant N-acetylcystein (NAC) before allergen challenge. Inflammatory infiltration and remodelling were assessed 48 h after allergen challenge. RESULTS: ROS generation was increased by 3.7-fold, which was inhibited by SR 140333. [Sar(9),Met(11)(O(2))]-Substance P (5 nM) caused a tachykinin NK-1 receptor-dependent fourfold increase in ROS generation. Epithelial proliferation was decreased by 68% by incubation with [Sar(9),Met(11)(O(2))]-SP over 72 h. In-vivo, treatment with SR 140333 and NAC reduced epithelial damage (91.4% and 76.8% vs. placebo, respectively, P<0.01) and goblet cell hyperplasia (67.4% and 50.1% vs. placebo, respectively, P<0.05), and decreased inflammatory cell influx (65.3% and 45.3% vs. placebo, respectively, P<0.01). CONCLUSION: Allergen challenge induces ROS in a tachykinin NK-1 receptor-dependent manner. Inhibition of the tachykinin NK-1 receptor reduces epithelial damage and subsequent remodelling in vivo. Therefore, patients may possibly benefit from treatment regime that includes radical scavengers or tachykinin NK-1 receptor antagonists.


Assuntos
Células Epiteliais/metabolismo , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia , Pneumonia/metabolismo , Pneumonia/patologia , Espécies Reativas de Oxigênio/metabolismo , Receptores da Neurocinina-1/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C
18.
J Chemother ; 19(3): 309-14, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17594927

RESUMO

Central Venous Catheters (CVC) and ports are essential devices to the medical care of cancer patients. Every year about one million CVCs are inserted in cancer patients. The field of oncohematology is making a great contribution to the development of new models of catheters and to the use of innovative materials. New therapeutic protocols, based on continuous administration and higher doses of anticancer drugs with relative phlebitis problems, have raised the issue of long CVC in situ permanence. Different complications are related to the intravascular catheters such as those associated with insertion (pneumothorax, damages to arteries and nerves), or with the duration of catheterization (thrombosis and infections). Furthermore, Catheter-Related Bloodstream Infections (CRBSI), in particular, cause significant mortality and excessive hospital costs. The aim of this prospective study was to analyze the costs related to the use of polyurethane (PU) CVC. 44 patients with a non tunneled double lumen PU CVC in place were followed for 6 months, and for each patient, time of permanence, possible antibiotic prophylaxis, blood parameters, adverse events and medical treatments were monitored. Our results suggest that physicians should pay greater attention to the correlation between new medical devices and the real benefit for the patient, and economic consequences.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/economia , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateteres de Demora/efeitos adversos , Cateteres de Demora/economia , Custos e Análise de Custo , Infecção Hospitalar/etiologia , Infecção Hospitalar/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Trombose/etiologia , Trombose/prevenção & controle
19.
Trends Neurosci ; 17(12): 509-12, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7532332

RESUMO

The data reviewed in this article suggest that protons should no longer be considered simply as an unwanted by-product of anaerobic respiration that results from either an accumulation of inflammatory cells or a reduced oxygenated blood supply during ischaemia. A fall in extracellular pH can stimulate a subpopulation of sensory nerves by activation of ion channels. The available evidence indicates that most, if not all, of the activated neurones are also stimulated by capsaicin, and that protons and capsaicin share a common mechanism of neuronal activation. A proton should be viewed as a mediator that elicits a protective response with reflex cardiovascular and respiratory responses, which modulate systemic blood flow, and with the local release of sensory neuropeptides, which vasodilates the microvasculature and stimulates extravasation.


Assuntos
Capsaicina/farmacologia , Neurônios Aferentes/metabolismo , Prótons , Rutênio Vermelho/farmacologia , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/fisiologia , Capsaicina/agonistas , Capsaicina/antagonistas & inibidores , Eletrofisiologia , Cobaias , Neurocinina A/metabolismo , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/fisiologia , Ratos , Substância P/metabolismo
20.
Trends Neurosci ; 24(12): 687-90, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11718856

RESUMO

Neuropeptides 2001, 2nd Joint Meeting of the European Neuropeptide Club and the American Summer Neuropeptide Conference (11th Annual Meeting). 6-11 May 2001 with Satellite Symposium, Israeli-French Symposium, Israel Ministry of Science, Culture and Sport, 6 May 2001, held at Maale Hachmicha and Tel Aviv University, Israel.


Assuntos
Química Encefálica/fisiologia , Neuropeptídeos/fisiologia , Animais
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