Comparative study of the antihypertensive effects of hexane, chloroform and methanol fractions of essential oil of Alpinia zerumbet in rats Wistar / Estudo comparativo do efeito anti-hipertensivo das frações hexânixa, clorofórmica e metanólica do óleo essencial da Alpinia zerumbet

ABSTRACT The aim of this study was to characterize components of the EOAz and its hexane (HFEOAz), chloroform (CFEOAz) and methanol (MFEOAz) fractions, and its antihypertensive effect. EOAz was extracted from leaves by hydrodistillation. Aliquot was subjected to selective desorption with silica gel column and eluted with hexane, chloroform and methanol. The components of the EOAz and fractions were analyzed by gas chromatography coupled with mass spectrometry and nuclear magnetic resonance spectroscopy of hydrogen. Experiments of vascular reactivity were performed with isolated aortic rings of male Wistar rats. Antihypertensive effect was evaluated in hypertensive rats submitted to the inhibition of synthesis of nitric oxide. Blood pressure was measured indirectly by tail plethysmography. MFEOAz showed the lowest EC50 (150.45 µg/mL), 1,8-cineole (27.81%) and terpinen-4-ol (57.35%) as main components. Single administration by nasogastric tube of EOAz, fractions and captopril significantly reduced the blood pressure of hypertensive rats, when compared to animals of the negative control group with distilled water. In conclusion, the potency of the MFEOAz was higher than that of EOAz and other fractions. The antihypertensive effect of EOAz and fractions was similar, higher than the negative control and lower than that of captopril.

RESUMO O objetivo deste estudo foi caracterizar os componentes do óleo essencial das folhas de Alpinia zerumbet (OEAz) e suas frações hexânica (FHOEAz), clorofórmica (FCOEAz) e metanólica (FMOEAz), e seu efeito anti-hipertensivo. OEAz foi extraído das folhas por hidrodestilação. Uma alíquota foi submetida à desadsorção seletiva com coluna de gel de sílica e eluída com hexano, clorofórmio e metanol. Os componentes do OEAz e fracções foram analisadas por cromatografia gasosa acoplada à detector de massa e por espectros de ressonância magnética nuclear de hidrogênio. Experimentos de reatividade vascular foram realizados com anéis aórticos isolados de ratos Wistar machos. Efeito anti-hipertensivo foi avaliado em ratos hipertensos submetidos à inibição da síntese de óxido nítrico. A pressão arterial foi medida indiretamente por pletismografia de cauda. FMOEAz mostrou a menor CE50 (150,45 μg/mL), 1,8-cineol (27,81%) e terpinen-4-ol (57,35%) como componentes principais. A administração em dose única por sonda nasogástrica de OEAz, frações e captopril reduziu significativamente a pressão arterial de ratos hipertensos, quando comparados aos animais do grupo controle negativo com água destilada. Em conclusão, a potência da FMOEAz foi maior que a do OEAz e outras frações. O efeito anti-hipertensivo de OEAz e frações foi semelhante, maior do que o controle negativo e menor do que o captopril.

Headache in patients with idiopathic intracranial hypertension: a pilot study to assess applicability of ICHD-2 diagnostic criteria.

Headache is one of the most common symptoms of idiopathic intracranial hypertension (IIH). The aim of this study was to investigate the applicability of the diagnostic criteria for "Headache attributed to IIH" included in the current classification of headache disorders, particularly as far as the main headache features. A consecutive clinical series of IIH patients with demonstration of increased intracranial pressure by lumbar puncture in the recumbent position were enrolled. Among a total of 22 patients, headache was reported by 14. The proportion of patients reporting the main headache features required by diagnostic criteria were: 93 % for daily or nearly-daily occurrence; 71.5 % for diffuse/non-pulsating pain; 57 % for aggravation by coughing/straining. Thus, these three headache features, at least one of which is required for diagnosis of headache attributed to IIH, were present in the vast majority of our sample, suggesting that their inclusion should be regarded as appropriate. The analysis of our results may suggest possible changes in the current ICDH-2 criteria for headache attributed to IIH, based on the following considerations: the existence of remarkable differences as far as the relative frequency of each headache feature; the fact that diffuse and non-pulsating pain-included in the current classification as a single requirement-were not always found together; the high frequency of migrainous associated symptoms (nausea or photophobia-phonophobia were present in 71.5 % cases).

Confiança e agregação de valor em carnes com indicação geográfica / Trust and added value on meat with geographic indication

O aumento da procura por produtos agroalimentares com certificação relacionada à origem geográfica tem ocorrido, buscando atender nichos específicos de mercado. Nesse sentido, este trabalho identificou a percepção dos consumidores brasileiros com relação às indicações geográficas e sua disposição em pagar por esse atributo. Como método, realizou-se uma survey utilizando-se o software Sphinx, via internet, com 272 consumidores de carne bovina. Constatou-se que a percepção do consumidor sobre as indicações geográficas em carnes é, de maneira geral, positiva, sendo este atributo reconhecido como um indicador de qualidade. Os consumidores entrevistados acreditam que essas carnes oferecem maior segurança alimentar e são mais confiáveis que o produto sem a indicação de origem geográfica, sendo possível agregar valor em função de tais diferenciais. Além disso, o consumidor valorizou esse atributo e está disposto a pagar mais pelas carnes com selo de indicação geográfica.

The increased demand for agrifood products with certification related to the geographical origin has occurred on both global and national levels, seeking to meet specific market niches. In this sense, this article aims to identify consumer perceptions with respect to geographical indicators and their willingness to pay for this attribute. As a method, there was an internet survey among 272 consumers of beef with the help of the Sphinx software. It was found that consumer perception on geographical indications in meat is generally positive, and this attribute is recognized as a quality indicator. Consumers believe that this meat offers security and is more reliable than the product that doesn’t mention source, and you can add value to these differences. In addition, consumers value this attribute and are willing to pay more for meat with the seal of geographical indication.

Treatment of alterations in CSF dynamics.

Alterations of the intracranial pressure (ICP) may be present in several conditions. The aim of this brief review is to focus on two relatively rare conditions characterized by alterations in cerebro-spinal fluid dynamics--Spontaneous Intracranial hypotension (SIH) and Idiopathic Intracranial hypertension (IIH)--in which headache is one of the key symptoms. The most relevant clinical features, the expected MRI findings, and the therapeutic options regarding both conditions are discussed.

Psychopathological profile of patients with chronic migraine and medication overuse: study and findings in 50 cases.

Patients with chronic migraine (CM) have high frequence of psychiatric comorbidity or psychological distress. The presence of depression, anxiety, panic or obsessive disorders in these patients contributes to poor quality of life and can influence prognosis and treatment. A systematic investigation of psychiatric comorbidity is needed in patients with CM especially in those with medication overuse (MO), in order to reach a more comprehensive clinical management. We assessed the psychological profile of 50 patients, 40 women and 10 men suffering from CM with MO. The Spectrum Project, a complementary way of describing and assessing psychopathology with structured clinical interviews, was used for the psychological evaluation of the patients to explore personality traits. Spectrum instruments mood disorders (MOODS), panic agoraphobic disorders (PAS) and obsessive-compulsive disorder (OBS) were applied to study patients. OBS-questionnaire was positive in 28% of the patients, MOODS-questionnaire in 44%, PAS-questionnaire in 46%. 19 on 50 patients (38%) presented positivity to 2 or to all questionnaires in variable associations. None of the patients of the studied group had complete normal findings in the questionnaires. Clinical records of patients with OBS-questionnaire positivity showed a worse clinical course and tendency to relapse. These results suggest that psychological assessment is an essential step in the evaluation and treatment of patients with CM and MO. The remarkable percentage of OBS-questionnaire positivity in this group indicates that obsessive-compulsive trait represents besides depression and anxiety, a major risk of chronification and overusing.

Polytherapy for the prophylaxis of chronic migraine: an Italian survey.

Chronic migraine (CM) represents an important medical issue, due to morbidity, high disability, presence of comorbidities, and medication overuse (MO). The prophylaxis of CM has not been extensively explored so far. Patients with CM are often treated with two or more compounds, although there is no clear evidence that polytherapy may be superior to monotherapy. We evaluated the percentage of prescription of polytherapy for the prophylaxis of CM in a clinical sample. We examined the charts of 98 CM patients admitted to our Headache Center for inpatient withdrawal program to stop MO. Results showed that only one drug for prophylaxis was prescribed in 20.4% cases, two or more drugs in 79.6%, with 63.3% of the total sample falling in the group "true polytherapy", i.e. all the drugs prescribed on daily basis were given to treat CM, and not only to treat concomitant conditions. In more than 60% cases a combination of drugs indicated for migraine prophylaxis and drugs only indicated for other conditions (mainly for psychiatric disorders) was prescribed. Our survey indicates that polytherapy may be rather common in CM, and suggests that comorbidities may strongly influence treatment choices.

Clinical features and outcomes in spontaneous intracranial hypotension: a survey of 90 consecutive patients.

Spontaneous intracranial hypotension (SIH) is a rare disabling condition whose main clinical manifestation is orthostatic headache. We analysed clinical characteristics in relation to time to resolution in 90 consecutive patients diagnosed with SIH at our centre between 1993 and 2006. After excluding 7 patients lost to follow-up, the remaining 83 cases were divided into four groups: Group A (53 cases) with progressively worsening orthostatic headache; Group B (3 cases) with severe acute-onset orthostatic headache; Group C (9 cases) with fluctuating non-continuous headache, of mild severity, that, in 33% of cases, did not worsen on standing; Group D (18 cases), 5 with a previous history of headache, 14 with orthostatic headache, and 10 with altered neurological examination. Complete symptoms and neuroradiological resolution occurred during follow-up in Groups A, B and D, but was longer in Group D probably in relation to more severe clinical picture with altered neurological examination. However, after a mean of 52 months (range 24-108), none of the nine Group C patients had MRI indicating complete resolution. The main characteristic of Group C related to incomplete resolution was delayed diagnosis. These preliminary findings suggest that early diagnosis of SIH correlates with better outcome, further suggesting that patients with a new headache that may worsen on standing or sitting should undergo MRI with contrast to expedite a possible SIH diagnosis, even if the pain is relatively mild.

Costs of hypothalamic stimulation in chronic drug-resistant cluster headache: preliminary data.

In about 20% of chronic cluster headache (CH) cases, drugs may become ineffective. Under these circumstances, steroids and triptans are frequently employed leading to fearful side effects in one and high costs in the other. The direct costs of drug-resistant chronic CH are mainly due to frequent medical consultations and frequent use of expensive drugs. In recent years, hypothalamic stimulation has been employed to treat drug-resistant chronic CH patients suffering multiple daily attacks and long-term results from different centres show a 60% overall benefit. Nine years since the introduction of this technique, we attempt a preliminary analysis of the direct costs of hypothalamic stimulation based on patients treated at our centre. We estimated the following direct costs as follows: cost of neurosurgery plus cost of equipment (electrode, connection and impulse generator = 25,000 euro), cost of hospital admissions in long-term follow-up (2,000 euro per admission), cost of single sumatriptan injection (25 euro). Number of daily sumatriptan injections in the year before and for each year after hypothalamic implantation was obtained from headache diaries. To estimate the saving due to the reduction in sumatriptan consumption following hypothalamic stimulation, we calculated the following for each year of follow-up after surgery: number of sumatriptan injections in the year before surgery minus number of sumatriptan injections in each year, updated to December 2008. In our 19 implanted patients, the costs of neurosurgery plus cost of equipment were 475,000 euro; the costs of hospital admissions during follow up were 250,000 euro. Reduction in sumatriptan consumption resulted in a total saving of 3,573,125 euro. Hence, in our 19 patients, the sumatriptan saving (3,573,125 euro) minus the direct costs due to operation and follow up hospitalisations (475,000 + 250,000) euro is equal to 2,848,125 euro. These preliminary results indicate that hypothalamic stimulation is associated with marked reduction of direct costs in the management of complete drug-resistant chronic CH.

Application of IHS criteria to headache attributed to spontaneous intracranial hypotension in a large population.

We applied the recent International Headache Society (IHS) criteria for headache related to spontaneous intracranial hypotension (SIH) to 90 consecutive patients with a final diagnosis of SIH confirmed by cerebral magnetic resonance imaging with contrast. Orthostatic headache (developing within 2 h of standing or sitting up) was present in 67 patients (75%) but appeared within 15 min after standing or sitting-as required by point A of the criteria-in only 53 (59%). Forty-four (49%) patients did not satisfy point A, including 22 (24%) with non-orthostatic headache and 14 (16%) with headache developing >or= 15 min after standing or sitting up; 80 (89%) did not satisfy point D. Only three (3%) patients had headache fully satisfying the IHS criteria. These findings indicate that the current IHS criteria do not capture most patients with SIH-associated headache. Excluding the requirement for response to epidural blood patch (criterion D) and considering headaches appearing within 2 h of sitting or standing up would capture more patients.

Epidemiology of fixed unilateral headaches.

A fixed location unilateral headache suggests involvement of a precise nervous structure, and neuroimaging investigations are essential to seek to identify it. Nevertheless, side-locked primary headaches also occur, although they are rare. Side-locked primary headaches are more frequently found in the group of the short-lasting (

Functional neuroimaging and headache pathophysiology: new findings and new prospects.

In the last ten years pathophysiology of primary headaches has received new insights from neuroimaging studies. Positron emission tomography (PET) showed activation of specific brain structures, brainstem in migraine and hypothalamic grey in trigeminal autonomic cephalalgias. This brain activation suggests it may intervene both in a permissive or triggering manner and as a response to pain driven by the first division of the trigeminal nerve. Voxel-based morphometry has suggested that there is a correlation between the brain area activated specifically in acute cluster headache - the posterior hypothalamic grey matter - and an increase in grey matter in the same region. New insights into mechanisms of head pain have emerged thanks to neuroimaging obtained in experimentally induced headaches, and during peripheral and central neurostimulation.

Deep brain stimulation in craniofacial pain: seven years' experience.

Cluster headache (CH) is a primary headache with excruciatingly painful attacks that are strictly unilateral. About 10% of cases experience no significant remission, and about 15% of these do not respond to medication, so surgery is considered. Neuroimaging studies show that the posterior inferior hypothalamus is activated during CH attacks and is plausibly the CH generator. We report on 16 chronic CH patients, with headaches refractory to all medication, who received long-term hypothalamic stimulation following electrode implant to the posterior inferior hypothalamus. After a mean follow-up of 23 months, a persistent pain-free to almost pain-free state was achieved in 13/16 patients (15/18 implants; 83.3%) a mean of 42 days (range 1-86 days) after monopolar stimulation initiation. Ten patients (11 implants) are completely pain-free. A common side effect was transient diplopia, which limited stimulation amplitude. In one patient, a small non-symptomatic haemorrhage into the 3rd ventricle occurred following implant, but regressed 24 h later. Persistent side effects are absent except in one patient with bilateral stimulation, in whom stimulation was stopped to resolve vertigo and worsened bradycardia, but was resumed later without further problems. Hypothalamic stimulation is an effective, safe and well tolerated treatment for chronic drug-refractory CH. It appears as a valid alternative to destructive surgical modalities, and has the additional advantage of being reversible.

Validation of AIDA Cefalee, a computer-assisted diagnosis database for the management of headache patients.

AIDA Cefalee is a database for the management of headache patients developed on behalf of the Italian Neurological Association for Headache Research (ANIRCEF). The system integrates a diagnostic expert system able to suggest the correct ICHD-II diagnosis once all clinical characteristics of a patient's headache have been collected. The software has undergone a multicentre validation study to assess: its diagnostic accuracy; the impact of using the software on visit duration; the userfriendliness degree of the software interface; and patients' acceptability of computer-assisted interview. Five Italian headache centres participated in the study. The results of this study validate AIDA Cefalee as a reliable diagnostic tool for primary headaches that can improve diagnostic accuracy with respect to the standard clinical method without increasing the time length of visits even when used by operators with basic computer experience.

Headache and spontaneous low cerebrospinal fluid pressure syndrome.

We examined 59 consecutive patients presenting between 1993 and 2006 at our centre diagnosed with headache associated with spontaneous intracranial hypotension syndrome (SIH). Thirty-six (61%) patients were women; the mean age was 47 years (range 20-68). Cerebral MRI with contrast confirmed SIH in all patients. Headache characteristics were obtained by direct semistructured interview; in a minority of cases information was completed retrospectively through a phone call. All SIH patients suffered from headache. Early recognition of SIH may avoid dangerous worsening due to delayed diagnosis. Orthostatic headache, the main symptom, suggests the diagnosis.

Acute hypothalamic stimulation and ongoing cluster headache attacks.

Long-term hypothalamic stimulation is effective in improving drug-resistant chronic cluster headache (CH). We assessed acute hypothalamic stimulation to resolve ongoing CH attacks in 16 patients implanted to prevent chronic CH, investigating 136 attacks. A pain intensity reduction of > or =50% occurred in 25 of 108 evaluable attacks (23.1%). Acute hypothalamic stimulation is not effective in resolving ongoing CH attacks, suggesting that hypothalamic stimulation acts by complex mechanisms in CH prevention.

Neuroimaging and pain: a window on the autonomic nervous system.

Pain is one of the most common experiences of humans. Neuroimaging techniques can visualize the main brain areas involved in pain modulation, the pain matrix. It is noteworthy that many of the brain areas forming the pain matrix are also involved in modulating autonomic nervous system (ANS) activity that in turn plays a major role in determining the best adaptive response to the pain experience. The tight connection between the pain system and ANS is also evident from neuroanatomical studies indicating that the lamina 1 neurons receive both painful and visceral stimuli from all visceral organs giving rise to the spinothalamocortical pathway concerned with conveying interoceptive information to central structures. The resulting interoceptive stream projects to the viscerosensory cortex in the mid-insula and onto the right anterior insula and orbitofrontal cortices. Right anterior insula activation is involved in the sympathetic arousal associated with mental tasks. This brain region receives numerous other inputs including pain and painful stimuli are conveyed somatotopically to both insulae. A similar somatotopic organization of painful stimuli has also been shown in the basal ganglia involved in cognitive, affective, motor and autonomic states. This highly specialized organization of nociceptive information in these brain areas may subserve a number of functions, particularly of coupling pain with the most appropriate autonomic states and affective/emotional states. The anterior cingulated cortex, another brain area playing a crucial role in nociception, is also directly involved in the control of autonomic functions such as arousal during volitional behaviour, including effortful cognitive processing. It is evident that the nociceptive system and ANS closely interact in many processes involved in maintaining internal homeostatis and in order to give the most appropriate biological substrate for cognitive, affective and emotional states.

Deep brain stimulation and cluster headache.

In recent years, neuroimaging data have greatly improved the knowledge on trigeminal autonomic cephalalgias' (TACs) central mechanisms. Positron emission tomography studies have shown that the posterior inferior hypothalamic grey matter is activated during cluster headache attacks as well as in short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). Voxel-based morphometric MRI has also documented alteration in the same area in cluster headache patients. These data suggest that the cluster headache generator is located in this region and leads us to hypothesise that stimulation of this brain area could relieve intractable cluster headache just as deep brain stimulation improves intractable movements disorders. This view received support by the observation that high frequency stimulation of the ipsilateral hypothalamus prevented attacks in an otherwise intractable chronic cluster headache patient previously treated unsuccessfully by surgical procedures to the trigeminal nerve. So far, 16 patients with intractable cronic cluster headache (CCH) and one intractable SUNCT patient have been successfully treated by hypothalamic stimulation. The procedures were well tolerated with no significant adverse events. Hypothalamic DBS is an efficacious and safe procedure to relieve otherwise intractable CCH and SUNCT.

Spontaneous low cerebrospinal pressure: a mini review.

Spontaneous intracranial hypotension (SIH) is a syndrome of low cerebrospinal fluid (CSF) pressure characterised by postural headaches in patients without any history of dural puncture or penetrating trauma. Described by Schaltenbrand in 1938, SIH is thought to result from an occult CSF leak resulting in decreased CSF volume and, consequently, in low CSF pressure. Magnetic resonance imaging of the head and spine has improved the diagnosis of the syndrome showing peculiar radiographic abnormalities including diffuse pachymeningeal enhancement, subdural fluid collections and downward displacement of the cerebral structures. Treatment of SIH headache should start with conservative, non-invasive therapies while epidural blood patch has emerged as the treatment of choice for those symptomatic patients who have failed medical noninvasive approaches.

Headache and intracranial hypotension: neuroradiological findings.

The cardinal and classic features of postural headache and low cerebrospinal fluid (CSF) pressure in intracranial hypotension may not dominate the clinical picture of the syndrome and may be associated with additional various neurological symptoms and signs. Reports of unusual clinical presentations continue to appear in the literature. Despite the considerable variability of the clinical spectrum, neuroradiological studies reveal more constant and characteristic features. Brain MRI findings include intracranial pachymeningeal thickening and post-contrast enhancement, subdural fluid collections and downward displacement or "sagging" of the brain. Spinal MRI findings include collapse of the dural sac with a festooned appearance, intense epidural enhancement owing to dilatation of the epidural venous plexus, and possible epidural fluid collections. In fact, spinal studies may demonstrate CSF leakage from spinal dural defects, which are considered the most common cause of the syndrome. Myelo-MR may suggest the possible point of CSF leakage, by demonstrating an irregular root sleeve; myelo-CT and radioisotope myelocisternography (RMC) are often needed to confirm the point of CSF leakage. Neuroimaging studies are, therefore, essential for suggesting and confirming the diagnosis.

Strategies for the treatment of autonomic trigeminal cephalalgias.

Trigeminal autonomic cephalalgias (TACs) are a group of primary headache syndromes characterised by two main clinical characteristics: pain and oculofacial autonomic phenomena. Three headache forms are grouped as TACs: cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). These are distinguished mainly on the basis of attack duration. It lasts from 15 to 180 min in CH, from 2 to 30 min in PH and from 5 to 240 s in SUNCT. The most effective drug preventative in PH is indomethacin even if in few cases other non-steroidal anti-inflammatory drugs have been reported to be effective. SUNCT is commonly described as drug resistant. Recent studies report that lamotrigin may be the drug of choice for SUNCT.