A experiência de depressão na contemporaneidade: uma compreensão fenomenológico-existencial

The depression is one of the most common forms of getting ill nowaday. Due to the increase in incidence of depression cases registered worldwide, this theme has been the subject of important studies, especially regarding the symptomatological description and biological etiology of the disease. This research had the objective to understand the unique experience of depression experienced by people who recognize themselves in depression, under the focus of existential phenomenology of Martin Heidegger. To reach the proposed objective, individuals narratives interviews were conducted with four participants, starting from the triggering question, "from your experience, how is for you to being depressed?". The survey revealed that depression affects the whole person and is related to stressful life contexts. Depression was narrated as an experience of disempowerment and lack of self esteem and personal worth. The collaborators of the research referred to the depression from sad, angry, bored and pessimistic mood. The time is experienced as a restriction to the projective opening towards the possibilities of being in which the future is seen as catastrophic and the past lived as debt and guilt. The corporeality, in depression is experienced through the weight, fatigue and pains for no reason. The space is lived from the notion of fall and collapse. We also realized the desire for isolation and avoidance of social contact. Suicide is desired and represents the end of the suffering in life. The depression has proved, still, very stigmatized, because it is discredited and misunderstood. The stigma also addressed to the experience of hospitalization and the unsuitability to the socially imposed standards of beauty, which generates enough suffering to the depressed person. The medication was described based on its positive effects, as a balance and suffering reducer, but also as a producer of dependence. Were also identified according to the collaborators, traces of selfdemand, ordenality and being-for-others, characteristic of typus melancholicus. This study contributes to an understanding of the depression that goes beyond the merely biological perspective and symptomatology of the pathology. The investigation of the depressive experience, through the lens of Heidegger's phenomenology, showed us the phenomenon of the depression in their singularity, complexity and multiple meanings, showing the close relationship between the formation of the depression and the context of personal and social life of the participants

Freqüência e etiologia das dermatomicoses em pacientes atendidos no Hospital Giselda Trigueiro, Natal, RN

Dermatomycoses are fungal infections that attack the skin, hair and nails, in addition to the mucosal and cutaneous-mucosal zones. Objective: Observe the frequency of dermatomycoses, identify etiological agents and establish an association between the results and sex. Age, collection site, time and lesion location. Methods: Between February, 2002 and December, 2004, samples were collected from patients at Giselda Trigueiro Hospital in Natal, Brazil, by lesion scraping and hair removal, following 70% alcohol disinfection, and submitted to direct and culture examination. Results: Of the 817 lesions collected, 325 (39.8%) were fungus positive, with the hair collection site yielding the highest number of positive results (65.8%) and the scalp and hair representing the most frequent lesion sites (65.9%). Negative results occurred mainly in the lower limbs (78.6%). Of the species identified, 55.9% were yeasts, 41.6% dermatophytes and 2.5% Fusarium spp. Non-albicans Candida was the most isolated yeast (43.3%), mainly in females (61.7%) over the age of 40 years (56.4%). T. rubrum was the most isolated dermatophyte (67.9%),notably in males (59.2%) in the 0-20 age group (44.7%). With respect to collection site, 73.9% of the dermatophytes were present in the skin and 61.1% of the yeasts in the nails. When assessing the collection site, the inguinocrural regional was 22.6% positive for dermatophytes, and the nails and hands, 41.8% for yeasts. Conclusions: The results obtained verified that: most of the positive lesions were found in the hair, whereas skin and nail lesions yielded more negative results; T. rubrum was the most isolated dermatophyte and non-albicans candida the most commonly found yeast; positivity was greater in males in the 0-20 year age group at the skin site and in the inguinocrural region, while yeasts were more frequent in females in the over-40 age group at the nail sites

Análise de fatores clínico-demográficos, psicológicos, hormonais e genéticos na síndrome da ardência bucal e ardor bucal secundário

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Interações físicas e psicossociais em mulheres com fibromialgia

Fibromyalgia (FM) is a non-inflammatory rheumatic syndrome of unknown etiology, with symptoms of diffuse musculoskeletal pain and presence of specific anatomic sites called tender points. The symptoms are often associated with fatigue, sleep disturbances, morning stiffness, alterations in pain perception, anxiety and depression. Fibromyalgia exhibits a correlation between physical and behavioral symptoms, which have a negative influence on the quality of life of patients. Emotional skills are important factors since they are related to subjective well-being, personal productivity, social interaction and interpersonal relationships. We aim to describe the physical and psychosocial interactions in women with FM, showing the association between perceived social support and affect with symptoms of pain, functionality and mood. We will also describe a body representation of pain in women with FM. Data were collected over 3 years and the sample size ranged between studies. This is an exploratory cross-sectional study conducted with a convenience sample of 63 women with FM and 42 healthy women as a control group (CT), aged 20-76 years, recruited through spontaneous demand at Onofre Lopes University Hospital (HUOL) and the Clinical School of Physiotherapy of Universidade Potiguar (UNP). The Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), Social Support Scale (MOS), Hamilton Anxiety Scale and Scale of Positive and Negative Affect Schedule (PANAS), in addition to pressure algometry were used. For data analysis, we used parametric and non-parametric tests and a general linear model with adjustment variables and analysis of variance. A significant difference was found between pain threshold and tolerance, functionality, depression, anxiety, social support, and positive and negative affect between the groups. Affective states and social support were associated with anxiety, depression and functionality. A body was drawn representing pain with higher incidences in trapeze, supraspinatus and second ribs. The reason for studying sensory aspects, affective behavior and social support in FM patients opens perspectives for scientific and clinical research of this syndrome. Women with chronic pain such as FM appear to have altered mood states, less social support and affective dysfunctions, influencing the other symptoms of the syndrome

Avaliação do cortisol, dehidroepiandrosterona sulfato e dos perfis lipídico e imunológico e suas correlações com a sensibilidade dolorosa, depressão e funcionalidade em mulheres com fibromialgia na pós-menopausa

Fibromyalgia (FM) is a non-inflammatory rheumatic syndrome characterized by widespread musculoskeletal pain with palpable tender points, muscle stiffness, fatigue, and sleep disturbances. Patients with FM have hormonal changes that are directly correlated with symptoms of the syndrome. The neuroendocrine regulation may be impaired, with abnormalities in the hypothalamus-pituitary-adrenal (HPA) axis with various hormones showing changes in their levels. In women in fertile period, various gonadal hormones are associated with symptoms of the syndrome, but studies focusing only a population of women in post-menopausal period who do not use hormone replacement are rare. We developed an analytical cross sectional study to assess the plasma levels of cortisol and dehidroepiandrosterona sulfate (DHEA-S) with quimioluminescence method in a group of 17 women with FM and 19 healthy women in post-menopause who do not use hormone replacement and observe the correlation with the symptoms of pain through algometry, depression and physical functional capacity measured from the Beck Depression Index (BDI) and the Fibromyalgia Impact Questionnaire (FIQ). Three blood samples were collected in the morning (between 8:00 9:30) with an interval of 24 hours for the measurements of hormonal levels and biochemical profile. There were no immunological or lipid changes in patients with FM. Comparing the two groups, there is no difference in levels of cortisol and a tangential effect for DHEA-S (p=0,094) with the lowest levels in the FM. DHEA-S also correlated with pain threshold (r=0,7) and tolerance (r=0,65) in group FM. We found the presence of depressive state and low physical functional capacity in FM. It was also evident that women in post-menopausal period, DHEA-S should influence the symptoms of increased sensitivity to pain, but not the presence of depressive status and low physical functional

Efeitos do tratamento com lítio na memória aversiva, comportamentos relacionados à ansiedade e depressão e na expressão de BDNF em ratos

Lithium (Li) is the first choice to treat bipolar disorder, a psychiatric illness characterized by mood oscillations between mania and depression. However, studies have demonstrated that this drug might influence mnemonic process due to its neuroprotector, antiapoptotic and neurogenic effects. The use of Li in the treatment of cognitive deficits caused by brain injury or neurodegenerative disorders have been widely studied, and this drug shows to be effective in preventing or even alleviating the memory impairment. The effects of Li on anxiety and depression are controversial and the relationship of the effects of lithium on memory, anxiety and depression remain unknown. In this context, this study aims to: evaluate the effects of acute and chronic administration of lithium carbonate in aversive memory and anxiety, simultaneously, using the plus maze discriminative avoidance task (PMDAT); test the antidepressant effect of the drug through the forced swimming test (FS) and analyze brainderived neurotrophic factor (BDNF) expression in structures related to memory and emotion. To evaluation of the acute effects, male Wistar rats were submitted to i.p. administration of lithium carbonate (50, 100 or 200 mg/kg) one hour before the training session (PMDAT) or lithium carbonate (50 or 100 mg/kg) one hour before the test session (FS). To evaluation of the chronic effects, the doses administered were 50 or 100 mg/kg or vehicle once a day for 21 days before the beginning of behavioral tasks (PMDAT and FS). Afterwards, the animals were euthanized and their brains removed and submitted to immunohistochemistry procedure to quantify BDNF. The animals that received acute treatment with 100 and 200 mg/kg of Li did not discriminated between the enclosed arms (aversive and non-aversive) in the training session of PMDAT, showing that these animal did not learned the task. This lack of discrimination was also observed in the test session, showing that the animals did not recall the aversive task. We also observed an increased exploration of the open arms of these same groups, indicating an anxiolytic effect. The same groups showed a reduction of locomotor activity, however, this effect does not seem to be related with the anxiolytic effect of the drug. Chronic treatment with Li did not promote alterations on learning or memory processes. Nevertheless, we observed a reduction of open arms exploration by animals treated with 50 mg/kg when compared to the other groups, showing an anxiogenic effect caused by this dose. This effect it is not related to locomotor alterations since there were no alterations in these parameters. Both acute and chronic treatment were ineffective in the FS. Chronic treatment with lithium was not able to modify BDNF expression in hippocampus, amygdala and pre-frontal cortex. These results suggest that acute administration of lithium promote impairments on learning in an aversive task, blocking the occurrence of memory consolidation and retrieval. The reduction of anxiety following acute treatment may have prevented the learning of the aversive task, as it has been found that optimum levels of anxiety are necessary for the occurrence of learning with emotional context. With continued, treatment the animals recover the ability to learn and recall the task. Indeed, they do not show differences in relation to control group, and the lack of alterations on BDNF expression corroborates this result. Possibly, the regimen of treatment used was not able to promote cognitive improvement. Li showed acute anxiolytic effect, however chronic administration 4 promoted the opposite effect. More studies are necessary to clarify the potential beneficial effect of Li on aversive memory

Padronização de testes para avaliação do estado de mania e potencial anti-maníaco de um agonista do receptor NOP

Bipolar disorder is characterized by mood impairment, alternating between mania/hypomania and depression, and its exact pathophysiology is already unknown. The treatment of bipolar disorder is based on prevention of the manic and depressive episodes using mood stabilizers. Nociceptin/orfanin FQ (N/OFQ) is an endogenous heptadecapeptide which binds as an agonist to NOP receptor, which is a G-coupled inhibitory receptor. N/OFQ and its receptor modulate a lot of functions in the organism, including emotional processes. It is known that the plasmatic concentration of N/OFQ is altered in patients in both phases depressive and manic of bipolar disorder and it is assumed that this system has a role on the etiology of this disorder. Concerning mania, the animal models used in research tend to focus in an unique aspect of the manic behavior, as hyperactivity or agressivity. In the 60’s, the hole board test was proposed, and it consists of an apparatus with holes where a behavior known as head-dippings is measured. High levels of head-dippings are suggestive of neophilia, while low levels can be characteristic of an anxious-like behavior. As the increase of exploratory and goal-directed behavior are characteristics of manic behavior, this test could help in mania research. Thus, this work was organized in 3 steps and aims to: (1) investigate the induction of a manic-like state promoted by ouabain, a Na+/K+-ATPase inhibitor, in the mouse open field test; (2) set up the hole board as a test to measure manic-like behaviors; and (3) investigate the N/OFQ effects in prevention of this kind of behavior on hole board. Male Swiss mice were used in this study, and they take part of only one of the described steps. Depending on the step performed, mice received one or more of the following treatments: (1) ouabain 10-6 , 10-5 , 10-4 , 10-3 or 10-2 M, intracerebroventricular (icv); (2) sodium valproate 300 mg/kg, intraperitoneal (ip); (3) sodium valproate 400 mg/kg, ip; (4) diazepam 1 mg/kg, ip; (5) methylphenidate 10 mg/kg, ip; and (6) N/OFQ 0,1 or 1 nmol, icv. The results suggest that hole board can be used to evaluate a manic state, through analysis of different animal behaviors. However, it was not possible to standard the model of Na+ /K+ -ATPase dysfunction through ouabain administration in mice. Moreover, the data suggest that N/OFQ, at the doses tested, has not affected the methylphenidate-induced mania-like behavior. Taken together, the results point to a new approach of manic research, through the hole board using. However, more studies are necessary in order to verify the role of N/OFQ system on bipolar disorder.

Características psicológicas do paciente obeso grave e suas implicações pós-operatórias na cirurgia bariátrica

Obesity is a chronic disease that has multi-factorial aetiology, characterized by high degree of body fat; the degree of obesity will vary according to the Body Mass Index (BMI=m2 /kg). The severe degree of obesity is characterized by BMI>40 and it is regularly associated to endocrine-metabolic or mechanic clinical alterations, and to psychological disorders. Binge Eating (BE) results were overly high for this population. The Bariatric Surgery has been the treatment chosen by those diagnosed with severe obesity as this intervention provides prompt outcomes for loss of weight and clinical improvement conditions. However, recent research has acquiesced that after two years between 20% and 30% of people subject to this intervention gained weight. The main objective of this research is to assess the psychological and behavioral characteristics of those diagnosed with severe obesity that have been subject to Gastric Bypass Surgery in the past 24 months. Specific aspects were investigated: (1) characteristics of different personalities and diagnose of clinic and personality disorders; (2) BE and its relation with loss of weight; (2) the difference between the groups regarding post-surgery care, e.g. physical activity, psychological and dietician input. Method: 40 adults (women and men) aged 23 and 60 year-old who went through a bariatric surgery in the past 24 months, in the city of Natal-RN (Brazil); they were assembled in two groups n=20, Gain group displaying loss of < 50% of their initial surplus of weight, and the Loss group displaying loss of >50%. The research protocol is made of a socio-demographic questionnaire and 3 psychometric instruments: Rorschach – Comprehensive System; Millon Personality Inventory (MCMI-III); and the Binge Eating Scale (Escala de Compulsão Alimentar Periódica (ECAP). Through Rorschach significant differences between these groups were verified according to the kind of personality (EB) - more EB Extratensivo in Gain group and Intratensivo in Loss group – and the lack of control to express affect, increasing the answer for Color Pure at Group I. Concerning the people standardization, the sample as a whole tends to show psychic pain, denigrated selfperception, high levels of self-criticism, distorted perceptions, vulnerability to develop mood disorders and high scores regarding Suicide. MCMI-III results showed more clinic and personality disorders in Group I: Depressive Disorder and Schizotypal, Anxiety, Dysthymia, Major Depressive Disorder; Thought Disorder, Bipolar- Manic and Posttraumatic Stress Disorder. In relation to ECAP, the results indicated significant differences, showing increased BE results in Gain group. There were found significant differences between BE severity and the presence of clinic and personality disorders. Concerning the post-surgery care, the observed differences are statistically significant regarding physical activities with median-increased differences in Loss group. There is a difference between the initial weight and the time post-surgery, indicating that the higher the initial weight and the time after the surgery the higher the re-gain of weight post-surgery. Finally, the results show that the participants with more than 3 years of surgery will have Clinic and Major Depressive Disorders; Somatoform Disorder; Dysthymia. These results confirm prior studies related to BE post-surgery and re-gain of weight as well as the proneness of clinic disorders in severe obesity people. That means the results reinforce that the surgery process is a facet of the severe obesity treatment. The post-surgery process needs to be the main focus of attention and have a long-term input to sustain the care of the surgery results and the quality of life of the patients.

Relação do polimorfismo BDNF val66met e níveis periféricos de BDNF com a doença de Parkinson e sua sintomatologia

Neurodegenerative diseases are frequently studied due to the increasing number of cases associated with the populational ageing and to the impact on the conditions on the quality of life. Parkinson’s disease (DP) is the second most frequent neurodegenerative disease. Despite the fact that its etiology is not completely understood, it is known that DP is caused by environmental and genetic factors. Thus, the investigation of etiologic factors and mechanisms responsible for the changes that lead to DP may help early diagnostic and prevention. A possible association between DP and the common polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies with contrasting results. For this reason, the aim of this study is to investigate if the BDNF Val66Met polymorphism is related to susceptibility to DP in a cohort of Brazilian patients. Additionaly, we verify if the presence of the polymorphism implies in alterations in the BDNF whole blood concentrations, as well as variations in symptomatology. The sample comprised Brazilian patients accompanied by the neurology service of the Onofre Lopes University Hospital (HUOL) and healthy controls (CTRL). The motor aspects of DP were evaluated by Hoehn e Yahr Scale (HY), Unified Parkinson’s Disease Rating Scale (UPDRS) and Schwab & England Scale (SE). For the evaluation of non-motor symptoms were used the following instruments: Frontal Assessment Battery (BAF), Mini-Mental State Examination (MEEM), Beck Depression Inventory (IDB) and the Beck Anxiety Inventory (IAB). Blood samples were collected for BDNF Val66Met polymorphism genotyping and BDNF whole blood measurement. As expected, DP patients performed worse in motor, cognitive and emotional battery of questionnaires. Alleles distribution between DP and CTRL was not significantly different, but the A/G genotype was significantly associated with a protector factor for DP. In contrast, the G/G genotype was significantly associated with depression and anxiety development in DP patients. However, BDNF concentrations were not different between genotypes or groups. This is the first study of genetic association of this polymorphism with DP in Brazilian subjects and the first one that associate A/G genotype with protection against DP.

Sinalização endógena do sistema Nociceptina/Orfanina FQ - receptor NOP: envolvimento na modulação da depressão experimental induzida por lipopolissacarídeo

During the last decades, it has been established that there is a relationship between major depression and activation of immune system. Nociceptin/orphanin FQ (N/OFQ) is the natural ligand of a Gi-protein coupled receptor named NOP, both compose the peptidergic system wich is involved in the regulation of mood states and inflammatory responses. Considering these actions, the present thesis aimed to investigate the consequences of blocking NOP signaling in lipopolysaccharide (LPS)-induced sickness and depressive-like behaviors in mice. Systemic administration of LPS doses, that do not cause sepsis in mice, induce changes in their behaviors related with activity of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukins 6 (IL-6) and 1β (IL-1 β). At the time points of 2 to 6 h and 24 h after intraperitoneal injection, mice treated with LPS displayed, respectively, sickness and depressive-like behaviors. In the present work the administration of LPS 0.8 mg/kg (ip) significantly induced sickness signs in Swiss and CD-1 mice, such as weight loss, transient reduction in rectal temperature and decrease of food and water intake. Moreover at 24 h after LPS injection these same mice strains displayed significantly increased immobility time on the tail suspension test (TST) when compared with control mice, this alteration was not related with possible locomotion impairments as verified on the open field test. Treatment with Nortriptyline 30 mg/kg (ip, 60 min prior the TST) reduced the immobility time of control and LPS-treated mice and was used as standard antidepressant. The NOP receptor antagonist SB-612111 (10 mg/kg, ip), 30 min prior LPS, did not modify LPS-induced sickness signs and depressive-like behavior. However, when injected 24 h after LPS treatment, SB-612111 (ip, 30 min prior the TST) as well as the peptidergic NOP receptor antagonist UFP-101 (10 nmol/2μL, icv, 5 min prior the TST) significantly reversed the toxin effects. The protocol of LPS-induced depressive-like states was also tested in NOP receptor knockout mice (NOP(-/-)) and their respective wild types (NOP(+/+)). LPS evoked transient rectal temperature reduction in NOP(-/-) mice and loss of body weight, food and water intake reduction in both NOP(+/+) and NOP(-/-) mice. The consumption of water was significantly different due to the genotype. LPS injection induced transient changes in pro-inflammatory cytokines. At 6 h after LPS injection, serum levels of TNF-α were significantly increased in NOP(+/+) and NOP(-/-) mice, as the IL-6 levels were significantly increased just in NOP(+/+) serum. At 24 h after LPS treatment the pro-inflammatory cytokines had returned to the baseline levels in both genotypes. LPS treatment elicited depressive-like effects in NOP(+/+) but not in NOP(-/-) mice. The data obtained during the execution of this doctoral thesis reveal that pharmacological and genetic blockade of NOP signaling does not affect LPS evoked sickness signs while reversing depressive-like behavior. In conclusion, these results highlight the involvement of the peptidergic system N/OFQ - NOP receptor in the modulation of behaviors related to mood and activation of the immune system.

Efeitos in vivo e in vitro de agonistas parciais do receptor NOP: implicações para o tratamento da ansiedade, depressão e mania

Introduction: This study aimed to investigate the effects of the two peptide NOP partial agonists (UFP-113 and [F/G]N/OFQ(1-13)NH2) and the non peptide NOP partial agonist (AT-090) in the mouse emotional behavior as well as in the intracellular transduction pathways following the receptor binding. Methods: Male Swiss or CD-1 mice were used in this study together with NOP(+/+) and NOP(-/-) mice. The elevated plus maze (EPM) was used to evaluate the effects of compounds on anxiety-like behaviors. Diazepam and the NOP agonists, N/OFQ and Ro 65-6570, were used as positive controls in the EPM. NOP(+/+) and NOP(-/-) mice were used to evaluate the selectivity of those compounds that induced anxiolytic-like behaviors. The forced swim test (FST) was used to evaluate the effects of compounds on depressive-like behaviors. Nortriptyline and the NOP antagonists, UFP-101 and SB-612111, were used as positive controls in the FST. The effects of N/OFQ, UFP-101, SB-612111, UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090 were assessed in the methylphenidate-induced hyperlocomotion (MIH) test; in this assay valproate was used as positive control. The G protein and β-arrestin 2 transduction pathways of NOP receptor agonists (N/OFQ and Ro 65-6570), antagonist (UFP-101), and partial agonists (UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090) were also evaluated using an innovative assay that measures a bioluminescence resonance energy transfer process. For this, cell lines permanently co-expressing the NOP receptor coupled to luciferase (energy donor), and green fluorescent protein (energy acceptor) coupled to one of the effector proteins (G protein or β-arrestin 2) were used. Results: Diazepam (1 mg/kg), N/OFQ (1 nmol), Ro 65-6570 (0.1 mg/kg), and AT-090 (0.01 mg/kg) induced anxiolytic-like effect in mice in the EPM. The effects of Ro 65-6570 and AT-090 were selective to NOP receptor. UFP-113 (0.01-1 nmol) and [F/G]N/OFQ(1-13)NH2 (0.1-3 nmol) were inactive in the EPM. In the FST, nortriptyline (30 mg/kg), UFP-101 (10 nmol), SB-612111 (10 mg/kg), UFP-113 (0.01 and 0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (0.3 and 1 nmol) induced antidepressant-like effects, while AT-090 (0.001-0.1 mg/kg) was inactive in this assay. The effects of UFP-113 and [F/G]N/OFQ(1-13)NH2 were selective to NOP receptor. Valproate (400 mg/kg) counteracted methylphenidate (MPH, 10 mg/kg)-induced hyperlocomotion in mice in the open field. N/OFQ (1 nmol), UFP-113 (0.01-0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (1 nmol) were also able to reduce the MPH-induced hyperlocomotion, without changing the locomotor activity per se. The effect of UFP-113 was selective to NOP receptor. The UFP-101 (10 nmol), SB-612111 (10 mg/kg), and AT-090 (0.001-0.03 mg/kg) did not change the hyperlocomotor effect of methylphenidate. In vitro, N/OFQ and Ro 65-6570 behaved as NOP full agonists for G-protein and β-arrestin 2 pathways. AT-090 behaved as NOP receptor partial agonist for both transduction pathways, while UFP-113 and [F/G]N/OFQ(1-13)NH2 behaved as partial agonists and antagonists of NOP receptor for NOP/G protein and NOP/β-arrestin 2, respectively. UFP-101 behaved as NOP receptor antagonist for both transduction pathways. Conclusion: NOP ligands producing same effects on NOP/G protein interaction (partial agonism), but with opposite effects on β-arrestin 2 recruitment (partial agonism vs antagonism), can promote different in vivo effects on anxiety and mood as it was observed in the behavioral tests. This work corroborates the potential of NOP receptor as an innovative pharmacological target for the treatment of emotional disorders.

Efeitos in vivo e in vitro de agonistas parciais do receptor NOP: implicações para o tratamento da ansiedade, depressão e mania

Introduction: This study aimed to investigate the effects of the two peptide NOP partial agonists (UFP-113 and [F/G]N/OFQ(1-13)NH2) and the non peptide NOP partial agonist (AT-090) in the mouse emotional behavior as well as in the intracellular transduction pathways following the receptor binding. Methods: Male Swiss or CD-1 mice were used in this study together with NOP(+/+) and NOP(-/-) mice. The elevated plus maze (EPM) was used to evaluate the effects of compounds on anxiety-like behaviors. Diazepam and the NOP agonists, N/OFQ and Ro 65-6570, were used as positive controls in the EPM. NOP(+/+) and NOP(-/-) mice were used to evaluate the selectivity of those compounds that induced anxiolytic-like behaviors. The forced swim test (FST) was used to evaluate the effects of compounds on depressive-like behaviors. Nortriptyline and the NOP antagonists, UFP-101 and SB-612111, were used as positive controls in the FST. The effects of N/OFQ, UFP-101, SB-612111, UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090 were assessed in the methylphenidate-induced hyperlocomotion (MIH) test; in this assay valproate was used as positive control. The G protein and β-arrestin 2 transduction pathways of NOP receptor agonists (N/OFQ and Ro 65-6570), antagonist (UFP-101), and partial agonists (UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090) were also evaluated using an innovative assay that measures a bioluminescence resonance energy transfer process. For this, cell lines permanently co-expressing the NOP receptor coupled to luciferase (energy donor), and green fluorescent protein (energy acceptor) coupled to one of the effector proteins (G protein or β-arrestin 2) were used. Results: Diazepam (1 mg/kg), N/OFQ (1 nmol), Ro 65-6570 (0.1 mg/kg), and AT-090 (0.01 mg/kg) induced anxiolytic-like effect in mice in the EPM. The effects of Ro 65-6570 and AT-090 were selective to NOP receptor. UFP-113 (0.01-1 nmol) and [F/G]N/OFQ(1-13)NH2 (0.1-3 nmol) were inactive in the EPM. In the FST, nortriptyline (30 mg/kg), UFP-101 (10 nmol), SB-612111 (10 mg/kg), UFP-113 (0.01 and 0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (0.3 and 1 nmol) induced antidepressant-like effects, while AT-090 (0.001-0.1 mg/kg) was inactive in this assay. The effects of UFP-113 and [F/G]N/OFQ(1-13)NH2 were selective to NOP receptor. Valproate (400 mg/kg) counteracted methylphenidate (MPH, 10 mg/kg)-induced hyperlocomotion in mice in the open field. N/OFQ (1 nmol), UFP-113 (0.01-0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (1 nmol) were also able to reduce the MPH-induced hyperlocomotion, without changing the locomotor activity per se. The effect of UFP-113 was selective to NOP receptor. The UFP-101 (10 nmol), SB-612111 (10 mg/kg), and AT-090 (0.001-0.03 mg/kg) did not change the hyperlocomotor effect of methylphenidate. In vitro, N/OFQ and Ro 65-6570 behaved as NOP full agonists for G-protein and β-arrestin 2 pathways. AT-090 behaved as NOP receptor partial agonist for both transduction pathways, while UFP-113 and [F/G]N/OFQ(1-13)NH2 behaved as partial agonists and antagonists of NOP receptor for NOP/G protein and NOP/β-arrestin 2, respectively. UFP-101 behaved as NOP receptor antagonist for both transduction pathways. Conclusion: NOP ligands producing same effects on NOP/G protein interaction (partial agonism), but with opposite effects on β-arrestin 2 recruitment (partial agonism vs antagonism), can promote different in vivo effects on anxiety and mood as it was observed in the behavioral tests. This work corroborates the potential of NOP receptor as an innovative pharmacological target for the treatment of emotional disorders.

Associação da depressão e distúrbio do sono em pacientes com e sem disfunção temporomandibular

Objective: To evaluate the inter-relationship between TMD (temporomandibular disorder), depression and sleep disorder. Methods: This is a case-control study with questionnaires in 111 patients, allocated from the Dentistry Department of UFRN, Natal, Brazil, from September 2014 to June 2015, for evaluation of depressive symptoms through the BDI (Beck Depression Inventory); sleep disorder, the PSQI (Pittsburgh Sleep Quality Index) and DTM through the RDC / TMD (diagnostic criteria to search for DTM). All indexes were applied by a single examiner previously trained and calibrated. The collected data were analyzed with chi-square tests of Pearson (χ2) and the unconditional logistic regression. Results: women had a risk of 2.85 times more likely to develop TMD (p = 0.046). The OR (odds ratio) shows that sleep disturbance increases by 2.19 the chances of having TMD (p = 0.062) and depressive symptoms increase the risk by 3.16 times in developing dysfunction (p = 0.053). Conclusion: The data of this research allows us to conclude that patients with TMD, in this population, were more likely to develop changes in sleep and depressive symptoms.

Translocação bacteriana para o pulmão na icterícia obstrutiva experimental em ratos

RESUMO: Objetivo: Tem sido demonstrado que a icterícia obstrutiva provoca depressão do sistema imunológico, mudança no padrão de colonização bacteriana dos intestinos e passagem de bactérias da luz intestinal para a circulação porta e sistêmica. Estudo experimental em ratos procurou observar a possibilidade de translocação bacteriana para os pulmões após a ligadura do colédoco. Método: Foram utilizados 20 ratos Wistar pesando de 178 a 215g, separados aleatoriamente em dois grupos iguais. Nos ratos do grupo I foi feita a ligadura do colédoco e nos do grupo II apenas a manipulação do colédoco com pinça atraumática (sham operation). No sétimo dia de observação os animais foram mortos com superdose de anestésico, sangue foi colhido para dosagem de bilirrubinas e os pulmões ressecados sob condições assépticas. Metade de cada pulmão foi homogeneizada e semeada em meios de cultura ágar McConkey e ágar sangue. A outra metade serviu para exame histopatológico –coloração hematoxilina e eosina. Os dados foram analisados pelo teste t, com significância 0,05. Resultados: revelaram bilirrubina total em média 18,7±3,6 no grupo I e 0,7±0,2 no grupo II. No grupo I foram isoladas colônias de Klebsiela sp nos pulmões de 30% dos animais e E. coli em 20%, e os escores histopatológicos atingiram a média 6,2±2,08. No grupo II não foram detectadas bactérias nos pulmões e os escores do exame histopatológico atingiram 1,8±1,16. A diferença dos dados analisados mostrou-se significativa (p<0,05). Conclusões: Concluiu-se que a icterícia obstrutiva por ligadura do colédoco em ratos provocou translocação de germes Gram-negativos para os pulmões e resultou em alterações histopatológicas significativas.

Retinopatia de Purtscher-like e pancreatite aguda

Retinopatia de Purtscher-like é uma baixa súbita da visão associada à imagem de múltiplas áreas branco-amareladas (manchas algodonosas) e hemorragias no pólo posterior de ambos os olhos. O exato mecanismo da injúria ainda não é claro, mas provavelmente seria de natureza embólica. Tem sido descrita em uma variedade de condições, incluindo pancreatite aguda, síndrome de embolia gordurosa, insuficiência renal,nascimento (parto e pós-parto), desordens do tecido conectivo, entre outras. Serão relatados três casos de pancreatite aguda confirmada pelos exames laboratoriais e história clínica, associadas a alterações no exame do fundo de olho, compatíveis com esta retinopatia