Extra-gonadal steroids modulate non-breeding territorial aggression in weakly electric fish.

The neuroendocrine control of intraspecific aggression is a matter of current debate. Although aggression in a reproductive context has been associated with high levels of circulating androgens in a broad range of species, it has also been shown to occur during the non-breeding season when gonads are regressed and plasma steroid hormone levels are low. In mammals and birds the aromatization of androgens into estrogens plays a key role in the regulation of aggression in both the breeding and non-breeding seasons. This is the first study in a teleost fish to explore the role of steroids in the modulation of non-breeding aggression. Gymnotus omarorum is a highly aggressive teleost fish that exhibits aggression all year-round. We analyzed male-male non-breeding agonistic behavior, compared circulating 11-Ketotestosterone (11-KT) levels between dominants and isolated males, assessed the regulatory role of aromatization of androgens into estrogens, and evaluated the gonads as a source of these sex steroids. We found that high levels of aggression occurred in the non-breeding season despite low plasma 11-KT levels, and that there was no difference in 11-KT levels between dominant and isolated males. We demonstrated that acute aromatase inhibition decreased aggression, distorted contest dynamics, and affected expected outcome. We also found that castrated individuals displayed aggressive behavior indistinguishable from non-castrated males. Our results show, for the first time in teleost fish, that territorial aggression of G. omarorum during the non-breeding season depends on a non-gonadal estrogenic pathway.

The pharmacological treatment of migraine in Brazil.

BACKGROUND/OBJECTIVES: Migraine is a chronic, disabling, and recurrent illness. Despite its burden, preventive medications are often underused, while acute strategies are frequently used injudiciously. Patients may benefit from comprehensive approaches with general informative orientation and formal medication strategies. In developing countries like Brazil, the access to comprehensive tertiary headache centers or updated specialists is somewhat limited, as are the resources available out of some private specialty care clinics. In addition, centers from the public system may not deliver effective care. The aim of this review is to perform a general description of the pharmacological treatments of migraine in tertiary headache centers of Brazil. METHODS: The data of 4 public and 6 private tertiary centers under the care of 16 neurologists involved with headache assistance in different cities of Brazil were gathered. Answers to questions directed to headache specialists, and analyzing data from previous care of patients was used to estimate a description of the general pharmacological approach used in Brazilian centers. The therapeutic options adopted by general practitioners were not considered as those from other medical specialties and holistic medicine, which also treat migraine on a common basis. RESULTS: Estimated data of nearly 4800 patients from 16 neurologists acting in headache clinics from 2005 to 2013 were collected. Headache approach by specialists in Brazil is basically divided into 2 groups. The public services, which assist nonpaying patients, deliver traditional and noncomprehensive approaches as well as prescribe mostly monotherapy. Roughly 30% of their patients do not receive preventive treatments that are generally tricyclic antidepressants or ß-blockers. Private centers, which are usually where paying people attend, as well as a few public centers of excellence, use multidisciplinary approaches and combination of drugs, despite the usual allegation of scarce evidence. Nearly 90% of the patients from these centers receive the prescription of preventive treatments, which are generally tricyclic antidepressants and/or neuromodulators and/or ß-blockers. COMMENTS: There is no consensus on whether patients turning to private tertiary centers are different from those seen in public nonpaying services. However, since it is directly related to economic status and public services may render free specific medications as well as official dispensation of work, it may be argued that patients have less headache impact, and suboptimal care is delivered in these instances. As for the studied private centers as well as for the few public excellence centers, care provided is usually varied, includes a combination of drugs, and prevention is commonly used.

Consenso de expertos de la Asociación Colombiana de Neurología parael tratamiento preventivo y agudo de la migraña / Expert consensus on the preventive and acute treatment of migraine on behalf of the Colombian Association of Neurology

La migraña es la cefalea primaria de mayor impacto en la población general; de acuerdo conla información local se calcula que al menos 3 millones de personas en Colombia padecen esta condición,conduciendo esta entidad a alta carga y discapacidad.Objetivo: Determinar información unificada respecto al tratamiento preventivo y agudo de los pacientescon migraña. Se incluye información del tratamiento de la migraña crónica y su asociación al uso excesivo deanalgésicos.Materiales y métodos: Consenso de expertos mediante metodología virtual Delphi en dos rondas con el grupototal y una con el grupo desarrollador. Se hizo una revisión de la literatura para obtener información destinadaal diseño de preguntas con relevancia clínica. Se incluyeron neurólogos de las principales regiones del país.Resultados: Se debe ofrecer tratamiento preventivo a los pacientes que sufren por lo menos 6 días al mes dedolor de cabeza por migraña durante 6 a 12 meses de acuerdo con las condiciones clínicas de cada paciente.Topiramato, ácido valproico/divalproato de sodio, metoprolol, propranolol, amitriptilina, y flunarizina sonsugeridos como medicamentos de primera línea.Conclusiones: Se obtienen recomendaciones y sugerencias del tratamiento agudo y preventivo de los pacientescon migraña. Se presentan recomendaciones para el tratamiento de casos refractarios y del uso excesivode analgésicos...

Migraine is the primary headache with the highest impact in the general population. Accordingto local information, about 3 million people in Colombia suffer from this neurological condition leading tohigh burden and disability.Objective: To provide uniform information regarding the acute and preventive treatment of patients withmigraine. Information about chronic migraine, medication overuse was considered.Materials and methods: Expert consensus by using online Delphi methodology. Three rounds were carriedout, the whole group participated in two of them and the developer group in the total number of rounds. Areview of the literature was conducted to obtain academic support to design questions with clinical relevance.Neurologists from the main Colombian regions were included...

Influence of acute treatment with sibutramine on the sympathetic neurotransmission of the young rat vas deferens.

The effects of acute treatment with sibutramine on the peripheral sympathetic neurotransmission in vas deferens of young rats were still not evaluated. Therefore, we carried out this study in order to verify the effects of acute sibutramine treatment on the neuronal- and exogenous agonist-induced contractions of the young rat vas deferens. Young 45-day-old male Wistar rats were pretreated with sibutramine 6 mg/kg and after 4h the vas deferens was used for experiment. The acute treatment with sibutramine was able to increase the potency (pD2) of noradrenaline and phenylephrine. Moreover, the efficacy (Emax) of noradrenaline was increased while the efficacy of serotonin and nicotine were decreased. The maximum effect induced by a single concentration of tyramine was diminished in the vas deferens from treated group. Moreover, the leftward shift of the noradrenaline curves promoted by uptake blockers (cocaine and corticosterone) and ß-adrenoceptor antagonist (propranolol) was reduced in the vas deferens of treated group. The initial phasic and secondary tonic components of the neuronal-evoked contractions of vas deferens from treated group at the frequencies of 2 Hz were decreased. Moreover, only the initial phasic component at 5 Hz was diminished by the acute treatment with sibutramine. In conclusion, we showed that the acute treatment with sibutramine in young rats was able to affect the peripheral sympathetic nervous system by inhibition of noradrenaline uptake and reduction of the neuronal content of this neurotransmitter, leading to an enhancement of vas deferens sensitivity to noradrenaline.

Diretrizes da World Federation of Societies of Biological Psychiatry (WFSBP) para tratamento biológico de transtornos depressivos unipolares, 1ª parte: tratamento agudo e de continuação do transtorno depressivo maior / World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for biological treatment of unipolar depressive disorders, part 1: acute and continuation treatment of major depressive disorder

Estas diretrizes práticas para o tratamento biológico de transtornos depressivos unipolares foram desenvolvidas por uma Força-Tarefa internacional da Federação Mundial de Sociedades de Psiquiatria Biológica (WFSBP). O objetivo ao desenvolver tais diretrizes foi rever sistematicamente todas as evidências existentes referentes ao tratamento de transtornos depressivos unipolares e produzir uma série de recomendações práticas com significado clínico e científico, baseadas nas evidências existentes. Têm como objetivo seu uso por todos os médicos que atendam e tratem pacientes com essas afecções. Os dados usados para o desenvolvimento das diretrizes foram extraídos primariamente de várias diretrizes e painéis nacionais de tratamento para transtornos depressivos, bem como de metanálises e revisões sobre a eficácia dos antidepressivos e outras intervenções de tratamento biológico identificadas por uma busca no banco de dados MEDLINE e Cochrane Library. A literatura identificada foi avaliada quanto à força das evidências sobre sua eficácia e, então, categorizada em quatro níveis de evidências (A a D). Esta primeira parte das diretrizes abrange definição, classificação, epidemiologia e evolução dos transtornos depressivos unipolares, bem como tratamento das fases aguda e de manutenção. As diretrizes se referem primariamente ao tratamento biológico (incluindo antidepressivos, outros medicamentos psicofarmacológicos e hormonais, eletroconvulsoterapia, fototerapia, estratégias terapêuticas complementares e novas) de adultos jovens e também, embora em menor grau, de crianças, adolescentes e adultos idosos.

These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). This first part of the guidelines covers disease definition, classification, epidemiology and course of unipolar depressive disorders, as well as the management of the acute and continuation-phase treatment. These guidelines are primarily concerned with the biological treatment (including antidepressants, other psychopharmacological and hormonal medications, electroconvulsive therapy, light therapy, adjunctive and novel therapeutic strategies) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.

Lysine clonixinate versus dipyrone (metamizole) for the acute treatment of severe migraine attacks: a single-blind, randomized study / Clonixinato de lisina versus dipirona (metamizol) para o tratamento agudo de uma crise intensa de enxaqueca: estudo monocego e randomizado

BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAID) are effective to treat migraine attacks. Lysine clonixinate (LC) and dipyrone (metamizol) have been proven effective to treat acute migraine. The aim of this study was to evaluate the efficacy and tolerability of the intravenous formulations of LC and dipyrone in the treatment of severe migraine attacks. METHOD: Thirty patients (28 women, 2 men), aged 18 to 48 years with migraine according the International Headache Society (IHS) (2004) were studied. The patients were randomized into 2 groups when presenting to an emergency department with a severe migraine attack. The study was single-blind. Headache intensity, nausea, photophobia and side effects were evaluated at 0, 30, 60 and 90 minutes after the drug administration. Rectal indomethacin as rescue medication (RM) was available after 2 hours and its use compared between groups. RESULTS: All patients completed the study. At 30 minutes, 0 percent of the dipyrone group 13 percent of the LC group were pain free (p=0.46). At 60 and 90 minutes, 2 (13 percent) and 5 (33 percent) patients from the dipyrone group and 11 (73 percent) and 13 (86.7 percent) patients from the LC group were pain free (p<0.001). At 60 minutes, significantly more patients from the LC group were nausea-free (p<0.001). Regarding photophobia, there were no differences between groups at 60 minutes (p=0.11). The use of RM at 2 hours did not differ among groups (p=0.50). Pain in the site of the injection was reported by more patients of the LC group compared to the dipyrone group (p<0.0001). CONCLUSION: LC is significantly superior to dipyrone in treating severe migraine attacks. LC promotes significantly more burning at the site of the injection.

CONTEXTO E OBJETIVO: Antiinflamatórios não esteroidais (AINE) são eficazes no tratamento de crises de enxaqueca. O objetivo deste estudo foi comparar a eficácia e a tolerabilidade das apresentações injetáveis do clonixinato de lisina (CL) e da dipirona no tratamento de crises intensas de enxaqueca. MÉTODO: Trinta pacientes (28 mulheres, 2 homens), com idades entre 18 e 48 anos e enxaqueca de acordo com a Classificação Internacional de Cefaléias (2004) foram estudados. Os pacientes foram randomizados em 2 grupos ao se apresentarem em uma unidade de emergência, com uma crise intensa de enxaqueca. O desenho do estudo foi monocego. A intensidade da cefaléia, a presença de náusea e fotofobia e os efeitos colaterais foram avaliados e comparados na administração das drogas e após 30, 60 e 90 minutos. Indometacina retal foi disponibilizada como droga de resgate (DR) e seu uso comparado entre os grupos. RESULTADOS: Todos os pacientes completaram o estudo. Após 30 minutos, 0 por cento do grupo da dipirona e 13 por cento do CL encontravam-se sem cefaléia (p=0,46). Após 60 e 90 minutos, 2 (13 por cento) e 5 (33 por cento) do grupo da dipirona e 11 (73 por cento) e 13 (86,7 por cento) do grupo do CL encontravam-se sem cefaléia (p<0,001). Após 60 minutos, o CL foi mais eficaz que a dipirona em eliminar a náusea (p<0,001), mas não houve diferença quanto à melhora da fotofobia entre os grupos (p=0,11). Não houve diferenças entre os grupos que utilizaram DR (p=0,50). Dor no local da injeção foi apresentada por mais pacientes que usaram CL comparados aos da dipirona (p<0,001). CONCLUSÃO: O CL é significativamente superior a dipirona no tratamento de uma crise intensa de enxaqueca, mas resulta em mais queimação no local da injeção.

The use of combination therapies in the acute management of migraine.

BACKGROUND AND OBJECTIVES: Migraine is a highly prevalent neurological disorder with multiple peripheral and central mechanisms. Targeting a single mechanism for treating individual attacks as well as for performing the prophylaxis has been shown to be only partially effective. Recently, the role of combining agents for acute migraine treatment has gained attention and the combination of a triptan plus a non-steroidal anti-inflammatory drug (NSAID) has demonstrated better efficacy. This review focuses on the fundamentals of treating migraine attacks with two or more agents, and emphasizes the characteristics of the recently approved fixed combination sumatriptan-naproxen. METHODS: A PubMed search using the terms "migraine", "treatment", "acute", "triptans", "non-steroidal anti-inflammatory drugs", "sumatriptan", "naproxen", and "combination" was used. In addition, abstracts presented in the major meetings of the American Headache and the International Headache Societies along with the American Academy of Neurology were also evaluated. RESULTS: Although most of the few studies encountered were not controlled, there is a clear trend for better efficacy in combining triptans with NSAID. Additionally, the results of two recent large and controlled studies using fixed combinations of sumatriptan (50 mg and 85 mg) with 500 mg naproxen sodium confirm the initial observations of the clear superiority of this combination over the use of each agent alone. The differences in the endpoints 24-hour pain-relief response as well as pain-free and pain-relief parameters at 2-hour time-point are the most noticeable efficacy measures. Tolerability was not different between studied drugs. CONCLUSIONS: Combining triptans with NSAID and other agents for the acute treatment of migraine suggests better outcome efficacy measures than the use of single agents. The fixed combination of sumatriptan and naproxen sodium offers improved 2-hour and 24-hour benefits over monotherapy with each one these options. Recently issued FDA approval for marketing the combination (sumatriptan 50 mg-naproxen 500 mg) emphasizes the usefulness and safety of this new treatment for migraine attacks.

Cissampelos sympodialis Eichl. (Menispermaceae) inhibits anaphylactic shock reaction in murine allergic model

The murine model of OVA-induced immediate allergic reaction was used to evaluate the effectiveness of intraperitoneal sub-acute treatment with the leaf hydroalcoholic extract of Cissampelos sympodialis (AFL) in the anaphylactic shock reaction, IgE production and the background proliferative response. BALB/c mice treated with AFL ranging from 200 to 400 mg/kg/day for 5 days before and during OVA-sensitization strongly reduced the animal death and promoted reduction in total and OVA-specific serum IgE level. Spleen cells from AFL-treated sensitized animals showed a decreased proliferative background response when compared with non-sensitized animals. These results demonstrated that sub-acute intraperitoneal treatment with Cissampelos sympodialis extract has an anti-allergic effect.

Intravenous lysine clonixinate for the acute treatment of severe migraine attacks: a double-blind, randomized, placebo-controlled study.

BACKGROUND: Several nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective in the treatment of migraine. However, few commercially available NSAIDs can be administered IV. Lysine clonixinate (LC), an NSAID derived from nicotinic acid, has been proved effective in various algesic syndromes (eg, renal colic, muscular pain, nerve compression, odontalgia). The oral formulation of LC has been shown to be effective in the treatment of migraine of moderate severity. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of the IV formulation of LC in the treatment of severe migraine. METHODS: This double-blind, randomized, placebo-controlled, prospective study enrolled patients with severe migraine (without aura) as defined by the criteria of the International Headache Society. When patients presented to a neurology hospital with an outpatient headache unit (Instituto de Neurologia Deolindo Couto, Rio de Janeiro, Brazil) with a severe migraine attack that had lasted <4 hours, they were randomized to 1 of 2 groups (IV placebo [25 mL of 0.9% saline] or IV LC [21 mL of 0.9% saline plus 4 mL of LC 200 mg]). Headache intensity and adverse effects (AEs) were assessed before (0 minute) and 30, 60, and 90 minutes after study drug administration. Rescue medication was available 2 hours after study drug administration, and its use was compared between groups. RESULTS: Thirty-two patients (23 women, 9 men; mean [SD] age, 32 [2] years; range, 18-58 years) entered the study. Twenty-nine patients (21 women, 8 men; mean [SD] age, 32 [2] years; range, 18-56 years) completed the study. Three patients (all in the placebo group) did not complete the study (1 patient was unable to rate the pain severity after drug administration and 2 patients refused IV drug administration). Among study completers, 17 patients received LC and 12 placebo. At 30 minutes, 1 patient (8.3%) in the placebo group and 5 patients (29.4%) in the LC group were pain free; the between-group difference was not statistically significant. At 60 and 90 minutes, respectively, 3 (25.0%) and 5 (41.7%) patients in the placebo group and 12 (70.6%) and 14 (82.4%) patients in the LC group were pain free (P = 0.021 and P = 0.028 between groups at 60 and 90 minutes, respectively). Six patients (50.0%) in the placebo group and 1 patient (5.9%) in the LC group required rescue medication at 2 hours (P = 0.010 between groups). Three patients (25.0%) in the placebo group experienced AEs, including vomiting, dizziness, and malaise (1 patient [8.3%] each); 11 patients (64.7%) in the LC group experienced 1 AE, including burning pain at the injection site (5 patients [29.4%]), heartburn (4 patients [23.5%]), and dizziness and malaise (1 patient [5.9%] each) (P = 0.025). CONCLUSIONS: NSAIDs administered by the IV route cannot be used routinely in an outpatient environment, although an attempt to improve drugs in this class is clearly justified. This study demonstrated that IV LC was effective and well tolerated in the treatment of severe migraine attacks. This finding differs from results with the oral formulation, which is effective only in migraine of moderate severity.