Inducible nitric oxide synthase haplotype associated with migraine and aura

Migraine is a complex neurological disorder with a clear neurogenic inflammatory component apparently including enhanced nitric oxide (NO) formation. Excessive NO amounts possibly contributing to migraine are derived from increased expression and activity of inducible NO synthase (iNOS). We tested the hypothesis that two functional, clinically relevant iNOS genetic polymorphisms (C-1026 A-rs2779249 and G2087A-rs2297518) are associated with migraine with or without aura. We studied 142 healthy women without migraine (control group) and 200 women with migraine divided into two groups: 148 with migraine without aura (MWA) and 52 with aura (MA). Genotypes were determined by real-time polymerase chain reaction using the Taqman (R) allele discrimination assays. The PHASE 2.1 software was used to estimate the haplotypes. The A allele for the G2087A polymorphism was more commonly found in the MA group than in the MWA group (28 vs. 18%; P < 0.05). No other significant differences in the alleles or genotypes distributions were found (P > 0.05). The haplotype combining both A alleles for the two polymorphisms was more commonly found in the MA group than in the control group or in the MWA group (19 vs. 10 or 8%; P = 0.0245 or 0.0027, respectively). Our findings indicate that the G2087A and the C-1026 A polymorphism in the iNOS gene affect the susceptibility to migraine with aura when their effects are combined within haplotypes, whereas the G2087A affects the susceptibility to aura in migraine patients. These finding may have therapeutic implications when examining the effects of selective iNOS inhibitors.

A new NO donor failed to release NO and to induce relaxation in the rat basilar artery

Nitric oxide (NO)-donors are pharmacologically active substances that in vivo or in vitro release NO. Their most common side effect is headache caused by cerebral vasodilatation. We previously demonstrated that the new NO-donor Ru(terpy)(bdq)NO](3+) (Terpy), synthesized in our laboratory, induces relaxation of rat aorta. This study aimed to verify the effect of Terpy and sodium nitroprusside (SNP) in basilar artery. We conducted vascular reactivity experiments on endothelium-denuded basilar rings. The concentrations of iron (Fe) and ruthenium (Ru) complex were analyzed in basilar artery lysates after incubation with NO donors by mass spectrometry. We also evaluated the NO released from SNP and Terpy by using confocal microscopy. Interestingly, Terpy did not induce relaxation of the basilar artery. SNP induced relaxation in a concentration-dependent way. NO donors cross the membrane of vascular smooth muscle and entered the cell. In spite of its permeability, Terpy did not release NO in the basilar artery. Otherwise, SNP released NO in the basilar artery cells cytoplasm. Taken together, our results demonstrate that the new NO donor (Terpy) failed to release NO and to induce relaxation in the basilar artery. The NO donor SNP induces vascular relaxation due to NO release in the vascular smooth muscle cells. (C) 2011 Elsevier B.V. All rights reserved.

Safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension

Objective: To assess safety and efficacy of sitaxsentan 50 and 100 mg in patients with pulmonary arterial hypertension (PAH). Background: Sitaxsentan is a highly selective endothelin-A receptor antagonist that was recently withdrawn by the manufacturer because of a pattern of idiosyncratic liver injury. Methods: Before sitaxsentan withdrawal, this 18-week double-blind, placebo-controlled study randomized patients with PAH to receive placebo or sitaxsentan 50 or 100 mg once daily. The primary efficacy endpoint was change from baseline in 6-min walk distance (6MWD) at week 18. Changes in World Health Organization (WHO) functional class and time to clinical worsening (TTCW) were secondary endpoints. The primary efficacy analysis was powered for sitaxsentan 100 mg versus placebo. Results: Of 98 randomized patients, 61% were WHO functional class II at baseline. Improvement from baseline to week 18 in 6MWD occurred with sitaxsentan 100 but not 50 mg; a strong placebo effect was observed. At week 18, WHO functional class was improved or maintained in more patients receiving sitaxsentan 100 mg than placebo (P = 0.038); 0% versus 12% of patients deteriorated, respectively. TTCW was not significantly different for 100-mg sitaxsentan patients than placebo (P = 0.090). Adverse events (AEs) occurring more frequently with sitaxsentan (50 or 100 mg) included headache, peripheral edema, dizziness, nausea, extremity pain, and fatigue; most AEs were of mild or moderate severity. Conclusion: Sitaxsentan 100 mg improved functional class but not 6MWD in PAH patients who were mostly WHO functional class II at baseline. No patient receiving sitaxsentan 100 mg experienced clinical worsening; sitaxsentan was well tolerated. (C) 2011 Elsevier Ltd. All rights reserved.

Cefaleia em pacientes com dor crônica entrevistados na Unidade de Dor do Hospital Central de Maputo, Moçambique

JUSTIFICATIVA E OBJETIVOS: Nos últimos anos, a abordagem da dor crônica em Maputo, capital de Moçambique, ganhou espaço, com a construção da Unidade de Dor do Hospital Central. No continente africano existem poucos estudos epidemiológicos sobre dor crônica. Em Moçambique, nenhum estudo prévio foi publicado. O objetivo deste estudo foi descrever e analisar as características da cefaleia em pacientes com dor crônica entrevistados no referido hospital. MÉTODO: Participantes com dor crônica de acordo com critérios da International Association for the Study of Pain (IASP), maiores de 18 anos, fluentes em português foram incluídos. Dados demográficos, características da dor crônica e presença de cefaleia foram investigados. RESULTADOS: Cento e dezoito pacientes foram avaliados. Destes, 79 (66,9%) eram mulheres e 39 (33,1%) eram homens, com média de idade de 52,4 anos. Presença de cefaleia foi frequente entre estes pacientes (53/ 44,9%) embora esta não fosse necessariamente sua dor principal. Cefaleia foi o principal segundo sítio de dor. Migrânea foi diagnóstico em 14 (11,9%) pacientes, cefaleia tensional em 28 (23,8%), cefaleia cervicogênica em 9 (7,6%). CONCLUSÃO: Os dados revelam que nos pacientes com dor crônica na Unidade de Dor do Hospital Central de Maputo há prevalência de cefaleias semelhante àquela descrita na população em geral por outros estudos.

Temporomandibular disorders and parafunctional oral habits: an anamnestic study

OBJECTIVE: To assess the frequency and severity of the signs and symptoms of temporomandibular disorders (TMD), the frequency of parafunctional oral habits and the correlation between the variables by means of the patients' perception regarding their problem. METHODS: One hundred patients diagnosed with TMD, through a clinical examination of their masticatory system, answered the questions of a previously published protocol concerning the signs and symptoms most frequently reported in the literature. RESULTS: According to the results from the non parametric statistical analysis, the frequency for the following signs and symptoms was significant: Fatigue and muscle pain, joint sounds, tinnitus, ear fullness, headache, chewing impairment and difficulty to yawn (p<0.01) and otalgia (p<0.05). As to the parafunctional oral habits, there was a significant presence of teeth clenching during the day and night (p<0.01) and teeth grinding at night (p<0.05). The variable correlation analysis showed that there was a positive correlation between symptom frequency and severity; age was correlated with the presence of otalgia, cervical pain and teeth sensitivity, besides being correlated with muscle and joint pain severity. Habit frequency was negatively correlated with age. TMD duration was also positively correlated with the symptoms of tinnitus, ear fullness, muscle and joint pain. CONCLUSION: The study results showed that the anamnestic assessment using ProDTMMulti can predict the severity of the TMD case.

A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1) inactivated monovalent vaccines with different adjuvant systems

Methods We conducted a phase I, multicenter, randomized, double-blind, placebo-controlled, multi-arm (10) parallel study involving healthy adults to evaluate the safety and immunogenicity of influenza A (H1N1) 2009 non-adjuvanted and adjuvanted candidate vaccines. Subjects received two intramuscular injections of one of the candidate vaccines administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay before and 21 days after each vaccination. The three co-primary immunogenicity end points were the proportion of seroprotection >70%, seroconversion >40%, and the factor increase in the geometric mean titer >2.5. Results A total of 266 participants were enrolled into the study. No deaths or serious adverse events were reported. The most commonly solicited local and systemic adverse events were injection-site pain and headache, respectively. Only three subjects (1.1%) reported severe injection-site pain. Four 2009 influenza A (H1N1) inactivated monovalent candidate vaccines that met the three requirements to evaluate influenza protection, after a single dose, were identified: 15 μg of hemagglutinin antigen without adjuvant; 7.5 μg of hemagglutinin antigen with aluminum hydroxide, MPL and squalene; 3.75 μg of hemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 μg of hemagglutinin antigen with aluminum hydroxide and squalene. Conclusions Adjuvant systems can be safely used in influenza vaccines, including the adjuvant monophosphoryl lipid A (MPL) derived from Bordetella pertussis with squalene and aluminum hydroxide, MPL with aluminum hydroxide, and squalene and aluminum hydroxide.