Ad libitum consumption of milk supplemented with omega 3, 6, and 9 oils from infancy to middle age alters behavioral and oxidative outcomes in male mice

We tested the hypothesis that administration of omega (ω)-9, ω-3, and ω-6 to mice can prevent oxidative alterations responsible for behavioral and cognitive alterations related with aging. Twenty-eight-day-old mice received skim milk (SM group), SM enriched with omega oil mixture (EM group), or water (control group) for 10 and 14 months, equivalent to middle age. Mice were evaluated for behavioral alterations related to depression and memory and oxidative status [brain levels of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and myeloperoxidase (MPO)]. The 10-month EM group increased immobility time during the forced swimming test compared with control, indicating increased stress response. The 14-month SM- and EM-treated groups increased sucrose consumption compared with control, showing an expanded motivational state. The 14-month SM group decreased the number of rearings compared with the 14-month control and EM groups. The number of entries and time spent in the central square of the open field was higher in the 10-month EM group than in the control, revealing an anxiolytic-like behavior. TBARS decreased in the hippocampus and striatum of the 10-month EM group compared with the control. A similar decrease was observed in the striatum of the 10-month SM group. GSH levels were higher in all 14-month treated groups compared with 10-month groups. MPO activity was higher in the 14-month EM group compared with the 14-month control and SM groups, revealing a possible pro-inflammatory status. In conclusion, omega oils induced conflicting alterations in middle-aged mice, contributing to enhanced behavior and anxiolytic and expanded motivational state, but also to increased stress response and pro-inflammatory alterations.

Spatial variations in fish assemblage structure in a southeastern Brazilian reservoir / Variações espaciais na estrutura das assembléias de peixes em um reservatório do sudeste do Brasil

Abstract We assessed the fish assemblage structure and composition of Nova Ponte Reservoir (Araguari River, Upper Paraná Basin, Brazil). We observed significant differences in abundance (p = 0.0003), richness (p = 0.0005) and diversity (p = 0.02) between lacustrine and riverine zones of the reservoir. Nine species were significantly more abundant in the riverine region: Astyanax altiparanae, Astyanax gr. fasciatus, Galeocharax knerii, Hoplias intermedius, Hypostomus sp., Leporinus friderici, Leporinus obtusidens, Pimelodus maculatus and Schizodon nasutus. The results indicated a longitudinal gradient in the composition and abundance of fishes in Nova Ponte Reservoir, reinforcing the importance of freely flowing riverine reaches for conserving native neotropical ichthyofauna and reflecting the strong adaptation of these species to riverine systems.

Resumo Este estudo avaliou a assembléia de peixes do reservatório de Nova Ponte (rio Araguari, bacia do Alto Paraná, Brasil), em termos de estrutura e composição. Foram observadas diferenças significativas na abundância (p = 0.0003), riqueza (p = 0.0005) e diversidade (p = 0.02) entre as zonas lacustres e fluviais do reservatório. Nove espécies foram mais abundantes na região fluvial: Astyanax altiparanae, Astyanax gr. fasciatus, Galeocharax knerii, Hoplias intermedius, Hypostomus sp., Leporinus friderici, Leporinus obtusidens, Pimelodus maculatus and Schizodon nasutus. Os resultados indicaram a existência de um gradiente longitudinal na composição e abundância de peixes no reservatório de Nova Ponte. Estes padrões reforçam a importância de trechos fluviais livres de barramentos para a conservação da ictiofauna neotropical nativa e refletem a forte adaptação dessas espécies aos sistemas fluviais.

Cocos nucifera (L.) (Arecaceae): A phytochemical and pharmacological review

Cocos nucifera (L.) (Arecaceae) is commonly called the “coconut tree” and is the most naturally widespread fruit plant on Earth. Throughout history, humans have used medicinal plants therapeutically, and minerals, plants, and animals have traditionally been the main sources of drugs. The constituents of C. nucifera have some biological effects, such as antihelminthic, anti-inflammatory, antinociceptive, antioxidant, antifungal, antimicrobial, and antitumor activities. Our objective in the present study was to review the phytochemical profile, pharmacological activities, and toxicology of C. nucifera to guide future preclinical and clinical studies using this plant. This systematic review consisted of searches performed using scientific databases such as Scopus, Science Direct, PubMed, SciVerse, and Scientific Electronic Library Online. Some uses of the plant were partially confirmed by previous studies demonstrating analgesic, antiarthritic, antibacterial, antipyretic, antihelminthic, antidiarrheal, and hypoglycemic activities. In addition, other properties such as antihypertensive, anti-inflammatory, antimicrobial, antioxidant, cardioprotective, antiseizure, cytotoxicity, hepatoprotective, vasodilation, nephroprotective, and anti-osteoporosis effects were also reported. Because each part of C. nucifera has different constituents, the pharmacological effects of the plant vary according to the part of the plant evaluated.

Antidepressant-like effect of Hoodia gordonii in a forced swimming test in mice: evidence for involvement of the monoaminergic system

Hoodia gordonii is a plant species used traditionally in southern Africa to suppress appetite. Recently, it has been associated with a significant increase in blood pressure and pulse rate in women, suggesting sympathomimetic activity. The present study investigated the possible antidepressant-like effects of acute and repeated (15 days) administration of H. gordonii extract (25 and 50 mg/kg, po) to mice exposed to a forced swimming test (FST). Neurochemical analysis of brain monoamines was also carried out to determine the involvement of the monoaminergic system on these effects. Acute administration of H. gordonii decreased the immobility of mice in the FST without accompanying changes in general activity in the open-field test during acute treatment, suggesting an antidepressant-like effect. The anti-immobility effect of H. gordonii was prevented by pretreatment of mice with PCPA [an inhibitor of serotonin (5-HT) synthesis], NAN-190 (a 5-HT1A antagonist), ritanserin (a 5-HT2A/2C antagonist), ondansetron (a 5-HT3A antagonist), prazosin (an α1-adrenoceptor antagonist), SCH23390 (a D1 receptor antagonist), yohimbine (an α2-adrenoceptor antagonist), and sulpiride (a D2 receptor antagonist). A significant increase in 5-HT levels in the striatum was detected after acute administration, while 5-HT, norepinephrine and dopamine were significantly elevated after chronic treatment. Results indicated that H. gordonii possesses antidepressant-like activity in the FST by altering the dopaminergic, serotonergic, and noradrenergic systems.

Potencial terapêutico e uso de plantas medicinais em uma área de Caatinga no estado do Ceará, nordeste do Brasil / Therapeutic potential and use of medicinal plants in an area of the Caatinga in the state of Ceará, northeastern Brazil

O presente trabalho visou o levantamento etnobotânico das plantas medicinais, verificando a versatilidade das espécies utilizadas e o consenso de uso e/ou conhecimento entre os informantes, do Distrito de Aratama, no Município de Assaré, Ceará. As informações etnobotânicas foram obtidas através de entrevistas estruturadas e semi-estruturadas com os moradores locais. Foram citadas 116 espécies com fins medicinais pertencentes a 103 gêneros e 58 famílias com destaque para Fabaceae (10ssp.), Asteraceae (7spp.) e Lamiaceae (6spp.). Entre as espécies levantadas, Mentha spicata L., Rosmarinus officinalis L., Allium sativum L., Bauhinia cheilantha (Bong.), Ximenea americana L., se destacaram como as mais versáteis dentro da comunidade. As indicações terapêuticas citadas foram agrupadas em 16 categorias de sistemas corporais, dos quais as Desordens mentais e comportamentais, as Afecções ou dores não definidas, os Transtornos do sistema respiratório, as Doenças de pele e do tecido celular subcutâneo, e os Transtornos do sistema sensorial (ouvidos), mostram maior concordância entre os informantes na utilização de espécies para tratar um sistema corporal especifico. Os resultados mostraram elevada riqueza da flora medicinal presente na caatinga. Neste sentido, torna-se necessária a intensificação de estudos que avaliem e consolidem as propriedades químicas e farmacológicas destas espécies.

This study is about an ethnobotanical survey of medicinal plants, checking the versatility of the species used and the consensus of use and/or knowledge among informants from the Aratama District, in the municipality of Assaré, state of Ceará, Brazil. The ethnobotanical information was obtained through structured interviews and semi-structured interviews with local residents. Approximately, 116 species were mentioned for medicinal purposes, belonging to 103 genera and 58 families, especially Fabaceae (10ssp.), Asteraceae (7spp.) and Lamiaceae (6spp.). Among the surveyed species, Mentha spicata L., Rosmarinus officinalis L., Allium sativum L. and Bauhinia cheilantha (Bong.) Ximenea americana L. stood out as the most versatile in the community. The therapeutic indications mentioned were grouped into 16 categories of body systems; the mental and behavioral disorders, disorders or pain not defined, disorder of the respiratory system, skin diseases and subcutaneous tissue disorder, and disorder of the sensory system (ears) showed greater agreement among informants in the use of species to treat a specific body system. The results showed a high species richness of the medicinal flora present in the Brazilian Caatinga. Thus, it is necessary to intensify and consolidate studies assessing the chemical and pharmacological properties of these species.

Effect of image resolution manipulation in rearfoot angle measurements obtained with photogrammetry

The aim of this study was to investigate the influence of image resolution manipulation on the photogrammetric measurement of the rearfoot static angle. The study design was that of a reliability study. We evaluated 19 healthy young adults (11 females and 8 males). The photographs were taken at 1536 pixels in the greatest dimension, resized into four different resolutions (1200, 768, 600, 384 pixels) and analyzed by three equally trained examiners on a 96-pixels per inch (ppi) screen. An experienced physiotherapist marked the anatomic landmarks of rearfoot static angles on two occasions within a 1-week interval. Three different examiners had marked angles on digital pictures. The systematic error and the smallest detectable difference were calculated from the angle values between the image resolutions and times of evaluation. Different resolutions were compared by analysis of variance. Inter- and intra-examiner reliability was calculated by intra-class correlation coefficients (ICC). The rearfoot static angles obtained by the examiners in each resolution were not different (P > 0.05); however, the higher the image resolution the better the inter-examiner reliability. The intra-examiner reliability (within a 1-week interval) was considered to be unacceptable for all image resolutions (ICC range: 0.08-0.52). The whole body image of an adult with a minimum size of 768 pixels analyzed on a 96-ppi screen can provide very good inter-examiner reliability for photogrammetric measurements of rearfoot static angles (ICC range: 0.85-0.92), although the intra-examiner reliability within each resolution was not acceptable. Therefore, this method is not a proper tool for follow-up evaluations of patients within a therapeutic protocol.

Animal models of prenatal immune challenge and their contribution to the study of schizophrenia: a systematic review

Prenatal immune challenge (PIC) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism. Based on this, the goal of this article was to review the main contributions of PIC models, especially the one using the viral-mimetic particle polyriboinosinic-polyribocytidylic acid (poly-I:C), to the understanding of the etiology, biological basis and treatment of schizophrenia. This systematic review consisted of a search of available web databases (PubMed, SciELO, LILACS, PsycINFO, and ISI Web of Knowledge) for original studies published in the last 10 years (May 2001 to October 2011) concerning animal models of PIC, focusing on those using poly-I:C. The results showed that the PIC model with poly-I:C is able to mimic the prodrome and both the positive and negative/cognitive dimensions of schizophrenia, depending on the specific gestation time window of the immune challenge. The model resembles the neurobiology and etiology of schizophrenia and has good predictive value. In conclusion, this model is a robust tool for the identification of novel molecular targets during prenatal life, adolescence and adulthood that might contribute to the development of preventive and/or treatment strategies (targeting specific symptoms, i.e., positive or negative/cognitive) for this devastating mental disorder, also presenting biosafety as compared to viral infection models. One limitation of this model is the incapacity to model the full spectrum of immune responses normally induced by viral exposure.

Effects of different general anesthetics on serum hemolysis and hepatic and muscular glycogenolysis in rats

Anesthetics can affect the structure and biological function of tissues and systems differentially. The aim of the present study was to compare three injectable anesthetics generally used in experiments with animals in terms of the degree of hemolysis and glycogenolysis occurring after profound anesthesia. Twenty-four male Wistar rats (330-440 g) were divided into three groups (N = 8): chloral hydrate (CH), ketamine + xylazine (KX), Zoletil 50® (zolazepam and tiletamine) + xylazine (ZTX). After deep anesthesia, total blood was collected. The liver and white (WG) and red gastrocnemius (RG) muscles were also immediately removed. The degree of serum hemolysis was quantified on the basis of hemoglobin concentration (g/L). Hepatic and muscular glycogen concentrations (mmol/kg wet tissue) were quantified by the phenol-sulfuric method. The CH and KX groups exhibited serum hemolysis (4.0 ± 2.2 and 1.9 ± 0.9 g/L, respectively; P < 0.05) compared to the ZTX group, which presented none. Only KX induced elevated glycogenolysis (mmol/kg wet tissue) in the liver (86.9 ± 63.2) and in WG (18.7 ± 9.0) and RG (15.2 ± 7.2; P < 0.05). The CH and ZTX groups exhibited no glycogenolysis in the liver (164.4 ± 41.1 and 176.8 ± 54.4, respectively), WG (28.8 ± 4.4, 32.0 ± 6.5, respectively) or RG (29.0 ± 4.9; 25.3 ± 8.6, respectively). Our data indicate that ZTX seems to be an appropriate general anesthetic for studies that seek to simultaneously quantify the concentration of glycogen and serum biochemical markers without interferences. ZTX is reasonably priced, found easily at veterinary markets, quickly induces deep anesthesia, and presents a low mortality rate.

Ecodopplercardiograma na avaliação de sinais precoces de comprometimento cardíaco decorrente de diferentes níveis de hipertensão arterial sistêmica em pacientes de 18 a 40 anos / Dopplerechocardiography evaluation of early signs of cardiac involvement induced by several levels of systemic hypertension in individuals aged 18 to 40 years old

Objetivo: Avaliar as alterações precoces na função diastólica e morfologia cardíaca em pacientes com nível de hipertensão arterial primária entre 18 e 40 anos. Métodos: 110 pacientes normotensos e 130 hipertensos: 83 no estágio I (PAS - Pressão Arterial Sistólica de 140 a 159 mmHg e PAD (Pressão Arterial Diastólica de 90 a 99 mmHg); no estágio II (PAS de 160 a 179 mmHg, PAD de 100 a 109 mmHg) e 22 no estágio III (PAS acima de 180 mmHg e PAD acima de 110 mmHg) foram submetidos a exame físico e exames complementares (bioquímica, eletrocardiograma, raios-X de tórax e ecodopplercardiograma). Resultados: Nos hipertensos, a espessura do septo interventricular não foi significativamente maior, inclusive no estágio III (p maior 0,05). A espessura relativa da PP (parede posterior) definido pela relação PP / raio do VE (ventriculo esquerdo) em diastóle e a fração de ejeção só foram maiores em pacientes no estágio III (P menor 0,05). A massa do ventriculo esquerdo (MVE) e índice de massa do VE(IMVE) foram maiores em todos os grupos com hipertensão quando comparados aos normotensos. Pelo fluxograma da valva mitral, 92 por cento de pacientes com hipertensão estágio I, 83,9 por cento estágio II e 81,9 por cento estágio III tiveram uma relação E/A maior 1, como um dos indicadores de relaxamento VE normal. Hipertrofia concêntrica do VE foi significativamente maior em pacientes com hipertensão estágio III. Porém, hipertrofia excêntrica do VE foi maior em pacientes nos estágios II e I. Conclusão: A MVE e o IMVE foram as alterações mais frequentes em todos os estágios de hipertensão quando comparados aos normotensos, sugerindo ser a alteraçãio mais precoce e o achado mais sensível na avaliação de danos cardíacos a hipertensão entre 18 e 40 anos. A hipertrofia precede as alterções no relaxamento medida pela relação E/A no fluxograma da valva mitral, sugerindo ser não somente relacionada diretamente com idade e tempo de diagnóstico, ma também com o nível de pressão arterial.

Evaluation by blue native polyacrylamide electrophoresis colorimetric staining of the effects of physical exercise on the activities of mitochondrial complexes in rat muscle

Blue native polyacrylamide electrophoresis (BN-PAGE) is a technique developed for the analysis of membrane complexes. Combined with histochemical staining, it permits the analysis and quantification of the activities of mitochondrial oxidative phosphorylation enzymes using whole muscle homogenates, without the need to isolate muscle mitochondria. Mitochondrial complex activities were measured by emerging gels in a solution containing all specific substrates for NADH dehydrogenase and cytochrome c oxidase enzymes (complexes I and IV, respectively) and the colored bands obtained were measured by optique densitometry. The objective of the present study was the application of BN-PAGE colorimetric staining for enzymatic characterization of mitochondrial complexes I and IV in rat muscles with different morphological and biochemical properties. We also investigated these activities at different times after acute exercise of rat soleus muscle. Although having fewer mitochondria than oxidative muscles, white gastrocnemius muscle presented a significantly higher activity (26.7 ± 9.5) in terms of complex I/V ratio compared to the red gastrocnemius (3.8 ± 0.65, P < 0.05) and soleus (9.8 ± 0.9, P < 0.001) muscles. Furthermore, the complex IV/V ratio of white gastrocnemius muscle was always significantly higher when compared to the other muscles. Ninety-five minutes of exhaustive physical exercise induced a decrease in complex I/V and complex IV/V ratios after all resting times (0, 3 and 6 h) compared to control (P < 0.05), probably reflecting the oxidative damage due to increasing free radical production in mitochondria. These results demonstrate the possible and useful application of BN-PAGE-histochemical staining to physical exercise studies.

Effect of one-week ethanol treatment on monoamine levels and dopaminergic receptors in rat striatum

We studied the effects of ethanol on the levels of norepinephrine, dopamine, serotonin (5-HT) and their metabolites as well as on D1- and D2-like receptors in the rat striatum. Ethanol (2 or 4 g/kg, po) was administered daily by gavage to male Wistar rats and on the 7th day, 30 min or 48 h after drug administration, the striatum was dissected for biochemical assays. Monoamine and metabolite concentrations were measured by HPLC and D1- and D2-like receptor densities were determined by binding assays. Scatchard analyses showed decreases of 30 and 43 percent, respectively, in D1- and D2-like receptor densities and no change in dissociation constants (Kd) 48 h after the withdrawal of the dose of 4 g/kg. Ethanol, 2 g/kg, was effective only on the density of D2-like receptors but not on Kd of either receptor. Thirty minutes after the last ethanol injection (4 g/kg), decreases of D2 receptor density (45 percent) as well as of Kd values (34 percent) were detected. However, there was no significant effect on D1-like receptor density and a 46 percent decrease was observed in Kd. An increase in dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), a decrease in norepinephrine, and no alteration in 5-HT levels were demonstrated after 48-h withdrawal of 4 g/kg ethanol. Similar effects were observed in dopamine and DOPAC levels 30 min after drug administration. No alteration in norepinephrine concentration and a decrease in 5-HT levels were seen 30 min after ethanol (4 g/kg) administration. Our findings indicate the involvement of the monoaminergic system in the responses to ethanol

Training graduate students to be teachers

Pedagogic education of graduate students, when and where it exists, is restricted to theoretical courses or to the participation of the students as teachers' assistants. This model is essentially reproductive and offers few opportunities for any significant curriculum innovation. To open an opportunity for novelty we have introduced a new approach in "Biochemistry Teaching", a course included in the Biochemistry Graduate Program of the Biochemistry Department (Universidade Estadual de Campinas and Universidade de São Paulo). The content of the course consists of a) choosing the theme, b) selecting and organizing the topics, c) preparing written material, d) establishing the methodological strategies, e) planning the evaluation tools and, finally, f) as teachers, conducting the course as an optional summer course for undergraduate students. During the first semester the graduate students establish general and specific educational objectives, select and organize contents, decide on the instructional strategies and plan evaluation tools. The contents are explored using a wide range of strategies, which include computer-aided instruction, laboratory classes, small group teaching, a few lectures and round table discussions. The graduate students also organize printed class notes to be used by the undergraduate students. Finally, as a group, they teach the summer course. In the three versions already developed, the themes chosen were Biochemistry of Exercise (UNICAMP), Biochemistry of Nutrition (UNICAMP) and Molecular Biology of Plants (USP). In all cases the number of registrations greatly exceeded the number of places and a selection had to be made. The evaluation of the experience by both graduate and undergraduate students was very positive. Graduate students considered this experience to be unique and recommended it to their schoolmates; the undergraduate students benefited from a more flexible curriculum (more options) and gave very high scores to both the courses and the teachers.

Zinc and water intake in rats: investigation of adrenergic and opiatergic central mechanisms

We have demonstrated that central administration of zinc in minute amounts induces a significant antidipsogenic action in dehydrated rats as well as in rats under central cholinergic and angiotensinergic stimulation. Here we show that acute third ventricle injections of zinc also block water intake induced by central ß-adrenergic stimulation in Wistar rats (190-250 g). Central inhibition of opioid pathways by naloxone reverses the zinc-induced antidipsogenic effect in dehydrated rats. After 120 min, rats receiving third ventricle injections of isoproterenol (160 nmol/rat) exhibited a significant increase in water intake (5.78 ± 0.54 ml/100 g body weight) compared to saline-treated controls (0.15 ± 0.07 ml/100 g body weight). Pretreatment with zinc (3.0, 30.0 and 300.0 pmol/rat, 45 min before isoproterenol injection) blocked water intake in a dose-dependent way. At the highest dose employed a complete blockade was demonstrable (0.54 ± 0.2 ml/100 g body weight). After 120 min, control (NaAc-treated) dehydrated rats, as expected, exhibited a high water intake (7.36 ± 0.39 ml/100 g body weight). Central administration of zinc blocked this response (2.5 ± 0.77 ml/100 g body weight). Naloxone pretreatment (82.5 nmol/rat, 30 min before zinc administration) reverted the water intake to the high levels observed in zinc-free dehydrated animals (7.04 ± 0.56 ml/100 g body weight). These data indicate that zinc is able to block water intake induced by central ß-adrenergic stimulation and that zinc-induced blockade of water intake in dehydrated rats may be, at least in part, due to stimulation of central opioid peptides

Central lead administration inhibits water intake and sodium appetite in rats

We have demonstrated that acute third ventricle injections of lead acetate (PbAc) exert a powerful antidipsogenic effect and induce a significant increase in renal sodium excretion. In the present study we confirm the antidipsogenic effect of lead and demonstrate that central administration of this metal, in minute amounts, significantly reduces salt intake both during dehydration and after central angiotensinergic stimulation. Adult male Wistar rats had the third ventricle cannulated seven days before the experiments. During this period they had free access to distilled water and hypertonic saline solution (1.5 percent). After a 24-h period of fluid deprivation, experimental animals received third ventricle injections of PbAc (0.3, N = 8 and 3.0 nmol/rat, N = 14) while controls received sodium acetate (NaAc; 3.0 nmol/rat, N = 10). Rats treated with PbAc at the highest dose showed a significant reduction both in water and hypertonic saline intake when compared to controls. When the effect of lead administration on angiotensin II-induced water and salt intake was studied, normohydrated animals received third ventricle injections of angiotensin II (9.6 nmol/rat) after pretreatment with 3.0 nmol/rat of PbAc (experimental group, N = 10) or NaAc (controls, N = 8). The group pretreated with PbAc presented a significant reduction in both water and salt intake compared to controls. Thus, this study confirms the antidipsogenic effect of central lead injections and demonstrates that the presence of lead in the brain exerts a significant inhibition of sodium appetite

Lipoperoxidation associated with mitochondrial membrane permeabilization in the presence of Ca2+

Lipoperoxidation was investigated as a step for membrane protein thiol oxidation of rat liver mitochondria incubated in the presence of Ca2 and t-butylhydroproxide, by the determination of thiobarbituric acid reactive substances. Lipoperoxidation occured only when the incubation medium contained 125 µM t-butylhdroperoxide (t-buOOH) in the presence of Ca2+ and phosphate (Pi). No lipoperoxidation was observed when acetate replaced Pi as permeant anion, or when the oxidant was omitted, even at high Ca2 and Pi concentrations (up to 120 µMCa2+ and 5mMPi), conditions under which the mitochondria are fully permeabilized. In both cases, ADP protected efficiently against permeabilization, indicating the possible involvement of the ADP/ATP carrier in the earlier stages of the process

Narcolepsia: registro de um caso com estudo tomografico. / Narcolepsy: report of a case with tomographic study

Os autores relatam um caso de narcolepsia, no qual o paciente apos ser examinado sob o ponto de vista clinico, laboratorial, radiografico e eletroencefalografico, e submetido a tomografia computadorizada do encefalo. Discutem os aspectos clinicos, etiopatogenicos, hereditarios e terapeuticos da doenca, salientando a resposta favoravel ao uso da imipramina no controle dos sintomas