Comparison of the binding distribution of agonist and antagonist ligands for histamine H3 receptors in pig brain by quantitative autoradiography.

The relationship between the abundances of agonist and antagonist-binding sites for monoamine receptors is poorly established. Therefore, we used quantitative autoradiography to investigate the distribution and concentration of binding sites for histamine H(3) receptor ligands in cryostat sections of pig brain. As in other species, binding of the histamine H(3) receptor agonist [(3)H]N(alpha)-methylhistamine was highly heterogeneous in the pig brain, with highest B(max) in the substantia nigra, followed by the nucleus accumbens and caudate, intermediate binding in frontal cortex, diencephalon, and mesencephalon, and absent specific binding in cerebellum: the affinity of [(3)H]N(alpha)-methylhistamine was close to 1 nM in all regions of pig brain. Thus, the saturation binding parameters for this H(3) receptor agonist in pig brain were similar to the earlier reports in rat, guinea pig, and human. The distribution of histamine H(3) receptors labeled with the receptor antagonist [(125)I]iodophenpropit in adjacent cryostat sections from the same group of pigs was very similar to that of [(3)H]N(alpha)-methylhistamine. However, the B(max) of the receptor antagonist was 40% higher in the basal ganglia than was the B(max) of the receptor agonist. The K(d) for the receptor antagonist ligand was close to 0.9 nM in all regions. These results suggest that histamine H(3) receptor agonist-binding sites, i.e. those linked to intracellular G-protein, comprise a subset of the total receptor antagonist-binding sites in the basal ganglia, as has been reported for dopamine D(2) receptors.

Viral hepatitis: An alternative teaching method.

OBJECTIVES: Our teaching experience has shown that dealing with the immunological aspects of viral hepatitis poses several difficulties. Therefore, we developed a game to verify whether or not this active-learning exercise could enhance students' learning and arouse their interest in subjects that are basically complex. METHODS: Fifteen cards with clinical cases of hepatitis A, B, C, D, and E, and 50 explanatory cards with the description of epidemiological, clinical, and immunological aspects of the hepatitis mentioned above. The objective of the game was to match the explanatory cards with the respective clinical case. Pre- and post-tests were used to assess students' grade improvement. FINDINGS: One-hundred-and-forty students participated in the activity. The overall response of the students to the game was very positive: 129 (92.1%) found the game encouraged clinical thinking, and 105 (75%) regarded the game as an important way of consolidating learning. The students' grades significantly improved (p < 0.05). CONCLUSION: Games allow understanding the subject matter through global knowledge. They also foster the student-professor relationship, simplifying the solution to the questions that may arise from a more comprehensive study.

Distribution of PK11195 binding sites in porcine brain studied by autoradiography in vitro and by positron emission tomography.

The cerebral distribution of peripheral-type benzodiazepine binding sites (PBBS) in human brain has been investigated by positron emission tomography (PET) with the specific radioligand [11C]PK11195 in diverse neuropathological conditions. However, little is known about the pattern of PK11195 binding sites in healthy brain. Therefore, we used quantitative autoradiography to measure the saturation binding parameters for [3H]PK11195 in cryostat sections from young Landrace pigs. Specific binding was lowest in the cerebellar white matter (85 fmol mg(-1)) and highest in the caudate nucleus (370 fmol mg(-1)), superior colliculus (400 fmol mg(-1)), and anterior thalamic nucleus (588 fmol mg(-1)). The apparent affinity was in the range of 2-6 nM in vitro, predicting high specific binding in PET studies of living brain. However, the distribution volume (V(d), ml g(-1)) of high specific activity [11C]PK11195 was nearly homogeneous (3 ml g(-1)) throughout brain of healthy Landrace pigs, and was nearly identical in studies with lower specific activity, suggesting that factors in vivo disfavor the detection of PBBS in Landrace pigs with this radioligand. In young, adult Göttingen minipig brain, the magnitude of V(d) for [11C]PK11195 was in the range 5-10 ml g(-1), and had a heterogeneous distribution resembling the in vitro findings in Landrace pigs. There was a trend toward globally increased V(d) in a group of minipigs with acute MPTP-induced parkinsonism, but no increase in V(d) was evident in the same pigs rescanned at 2 weeks after grafting of fetal mesencephalon to the partially denervated striatum. Thus, [11C]PK11195 binding was not highly sensitive to constituitively expressed PBBS in brain of young Landrace pigs, and did not clearly demonstrate the expected microglial activation in the MPTP/xenograft model of minipigs.

Evaluation of defense mechanisms in adult patients with panic disorder: before and after treatment.

Patients with acute panic disorder (PD) use a more maladaptive pattern of defense mechanisms. This study investigated the use of defense mechanisms by patients with acute symptomatic PD and those in complete remission. Thirty-three patients and 33 controls were evaluated by the Mini International Neuropsychiatric Interview. The defense mechanisms were evaluated by the Defense Style Questionnaire at the beginning of the study and after 16 weeks of sertraline treatment. Panic disordered patients used more neurotic (4.6 vs. 3.6; p = 0.003) and immature (3.6 vs. 3.0; p = 0.024) defenses at baseline. Patients who achieved complete remission (N=25) differed from the control group in the use of neurotic defenses at the baseline (4.4 vs. 3.6; p = 0.033). After treatment, they showed a reduction in the use of neurotic (4.4 vs. 3.7; p=0.014) and immature (3.4 vs. 3.1; p = 0.019) defenses. Defense mechanisms in PD are influenced by the presence of symptoms, severity, and outcome of the disease.

Behavioral inhibition and history of childhood anxiety disorders in Brazilian adult patients with panic disorder and social anxiety disorder.

PURPOSE: To evaluate the presence of behavioral inhibition and anxiety disorders during childhood in Brazilian adult patients with panic disorder and social anxiety disorder compared to a control group. METHODS: Fifty patients with panic disorder, 50 patients with social anxiety disorder, and 50 control subjects were included in the study. To assess the history of childhood anxiety, the Schedule for Affective Disorders and Schizophrenia for School Age Children, Epidemiologic Version (K-SADS-E), and the Diagnostic Interview for Children and Adolescents-Parent Version (DICA-P) were used. The presence of behavioral inhibition in childhood was assessed by the self-reported scale of Behavioral Inhibition Retrospective Version (RSRI-30). RESULTS: Patients showed significantly higher prevalence of anxiety disorders and behavioral inhibition in childhood compared to the control group. Patients with social anxiety disorder also showed significantly higher rates of avoidance disorder (46% vs. 18%, p = 0.005), social anxiety disorder (60% vs. 26%, p = 0.001), presence of at least one anxiety disorder (82% vs. 56%, p = 0.009) and global behavioral inhibition (2.89 +/- 0.61 vs. 2.46 +/- 0.61, p < 0.05) and school/social behavioral inhibition (3.56 +/- 0.91 vs. 2.67 +/- 0.82, p < 0.05) in childhood compared to patients with panic disorder. CONCLUSION: Our data are in accordance to the literature and corroborates the theory of an anxiety diathesis, suggesting that a history of anxiety disorders in childhood is associated with an anxiety disorder diagnosis, mainly social anxiety disorder, in adulthood.

Behaviorial inhibition and history of childhood anxiety disorders in Brazilian adult patients with panic disorder and social anxiety disorder

OBJETIVOS: Avaliar a presença de história de comportamento inibido e de transtornos de ansiedade na infância em pacientes brasileiros adultos com transtorno do pânico e com transtorno de ansiedade social, comparando-os com um grupo controle. MÉTODOS: Cinqüenta pacientes com transtorno do pânico, 50 com transtorno de ansiedade social e 50 controles participaram do estudo. Para avaliar a presença de história de ansiedade na infância foi utilizada a Escala para Avaliação de Transtornos Afetivos e Esquizofrenia para Crianças em Idade Escolar - Versão Epidemiológica (K-SADS-E) e o Diagnostic Interview for Children and Adolescents-Parent Version (DICA-P). A presença de comportamento inibido na infância foi avaliada através da Escala Auto-Aplicativa de Comportamento Inibido - Versão Retrospectiva (RSRI-30). RESULTADOS: Os pacientes apresentavam uma prevalência significativamente maior de história de transtornos de ansiedade e de comportamento inibido em relação ao grupo controle. Pacientes com transtorno de ansiedade social apresentavam, também, taxas significativamente maiores de transtorno de evitação (46% x 18%, p = 0,005), transtorno de ansiedade social (60% x 26%, p = 0,001), presença de pelo menos um transtorno de ansiedade na infância (82% X 56%, p = 0,009), comportamento inibido global (2,89 ± 0,61 vs. 2,46 ± 0,61, p < 0,05) e comportamento inibido escola/social (3,56 ± 0,91 vs. 2,67 ± 0,82, p < 0.05) na infância em comparação com pacientes com transtorno do pânico. CONCLUSAO: Nossos dados são similares aos encontrados na literatura e corroboram a teoria da diátese de ansiedade, sugerindo que a história de transtornos de ansiedade na infância é associada com transtornos de ansiedade, principalmente transtorno de ansiedade social, na vida adulta.

Brazilian patients with panic disorder: the use of defense mechanisms and their association with severity.

This study aims to evaluate the defense mechanisms most frequently used by Brazilian patients with panic disorder when compared with a control group. The study also examines the association between severity of disease and comorbidity and the use of specific defense mechanisms. Sixty panic-disordered patients and 31 controls participated in the study. The Mini International Neuropsychiatric Interview was used to confirm the panic disorder diagnosis and to establish the comorbid diagnosis. The Clinical Global Impression (CGI) was used to assess severity and the Defensive Style Questionnaire (DSQ-40) was used to evaluate the defense mechanisms. Panic patients used more neurotic (mean = 4.9 versus 3.6; p < 0.001) and immature (mean = 3.9 versus 2.8; p < 0.001) defenses as compared with controls. Panic patients with severe disease (n = 37; CGI>4) had more depression comorbidity and used more immature defenses than patients with CGI

Stress regulates the lymphocyte homing receptor CD62L (L-selectin).

Based on a previous study showing that panic disorder patients had increased expression of na ve phenotype lymphocytes (CD45RA+ and CD62L+), increased plasma cortisol, as well as decreased interleukin-2 (IL-2) producion, we hypothesized that changes in the percentage of expression of these lymphocyte surface molecules could be related to the substances released by the hypothalamic-pituitary-adrenal (HPA) axis and possibly associated to panic disorder (cortisol, IL-2, serotonin and epinephrine). In order to study the altered expression, blood mononuclear cells of normal volunteers were stimulated with mitogen, in the presence of dexamethasone, IL-2, serotonin and epinephrin. CD62L is decreased by IL-2 in vitro. Serotonin and epinephrine did not promote changes in the expression of these surface molecules. The results of the ex vivo study are in agreement with a previous clinical study with panic patients. It could be suggested that stress is responsible for certain immunologic dysfunctions and new studies should be conducted.

Stress regulates the lymphocyte homing receptor CD62L (L-selectin)

Based on a previous study showing that panic disorder patients had increased expression of naïve phenotype lymphocytes (CD45RA+ and CD62L+), increased plasma cortisol, as well as decreased interleukin-2 (IL-2) producion, we hypothesized that changes in the percentage of expression of these lymphocyte surface molecules could be related to the substances released by the hypothalamic-pituitary-adrenal (HPA) axis and possibly associated to panic disorder (cortisol, IL-2, serotonin and epinephrine). In order to study the altered expression, blood mononuclear cells of normal volunteers were stimulated with mitogen, in the presence of dexamethasone, IL-2, serotonin and epinephrin. CD62L is decreased by IL-2 in vitro. Serotonin and epinephrine did not promote changes in the expression of these surface molecules. The results of the ex vivo study are in agreement with a previous clinical study with panic patients. It could be suggested that stress is responsible for certain immunologic dysfunctions and new studies should be conducted

Avaliação dos mecanismos de defesa em pacientes com fobia social: um estudo de caso-controle / Evolution of defense mechanisms in social phobic patients: a case-control study

Diversos estudos demonstram que o conhecimento de fatores psicodinâmicos é importante na avaliação e tratamento dos transtornos psiquiátricos. O objeivo desse estudo foi avaliar os mecanismos de defesa utilizados por pacientes adultos com fobia social comparados a um grupo de controle. Material e métodos: Trata-se de um estudo de caso-controle em que 35 pacientes com fobia social e 35 controles foram avaliados através do M.I.N.I. Os mecanismos de defesa foram aferidos através do DSQ-40. Resultados: Os pacientes com fobia social usam mais frequentemente defesas neuróticas e imaturas comparadas ao grupo controle (p<0,001). As defesas mais usadas por esses pacientes foram somatização e pseudo-altruísmo, seguidas de antecipação, cisão, fantasia, anulação, sublimação, racionalização e desvalorização. Conclusão: Os pacientes com fobia social possuem um perfil de mecanismos de defesas mais mal-adaptivo camparados aos controles, o que pode dificultar o tratamento dos mesmos.