PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes

Abstract Background Pituitary tumor transforming gene (pttg) is a novel oncogene that is expressed at higher level in most of the tumors analyzed to date compared to normal tissues. Nevertheless, its expression in prolactinomas and its relation with the pituitary dopamine receptor 2 (D2R) are not well defined. We sought to determine the pituitary level of pttg in three different experimental models of prolactinomas with altered dopaminergic control of the pituitary: the dopaminergic D2R knockout female mouse, the estrogen-treated rat, and the senescent female rat. These three models shared the characteristics of increased pituitary weight, hyperprolactinemia, lactotrope hyperplasia and reduced or absent dopaminergic action at the pituitary level. We also studied samples from human macroprolactinomas, which were characterized as responsive or resistant to dopamine agonist therapy. Results When compared to female wild-type mice, pituitaries from female D2R knockout mice had decreased PTTG concentration, while no difference in pttg mRNA level was found. In senescent rats no difference in pituitary PTTG protein expression was found when compared to young rats. But, in young female rats treated with a synthetic estrogen (Diethylstylbestrol, 20 mg) PTTG protein expression was enhanced (P = 0.029). Therefore, in the three experimental models of prolactinomas, pituitary size was increased and there was hyperprolactinemia, but PTTG levels followed different patterns. Patients with macroprolactinomas were divided in those in which dopaminergic therapy normalized or failed to normalize prolactin levels (responsive and resistant, respectively). When pituitary pttg mRNA level was analyzed in these macroprolactinomas, no differences were found. We next analyzed estrogen action at the pituitary by measuring pituitary estrogen receptor α levels. The D2R knockout female mice have low estrogen levels and in accordance, pituitary estrogen receptors were increased (P = 0.047). On the other hand, in senescent rats estrogen levels were slightly though not significantly higher, and estrogen receptors were similar between groups. The estrogen-treated rats had high pharmacological levels of the synthetic estrogen, and estrogen receptors were markedly lower than in controls (P < 0.0001). Finally, in patients with dopamine resistant or responsive prolactinomas no significant differences in estrogen receptor α levels were found. Therefore, pituitary PTTG was increased only if estrogen action was increased, which correlated with a decrease in pituitary estrogen receptor level. Conclusion We conclude that PTTG does not correlate with prolactin levels or tumor size in animal models of prolactinoma, and its pituitary content is not related to a decrease in dopaminergic control of the lactotrope, but may be influenced by estrogen action at the pituitary level. Therefore it is increased only in prolactinomas generated by estrogen treatment, and not in prolactinomas arising from deficient dopamine control, or in dopamine resistant compared with dopamine responsive human prolactinomas. These results are important in the search for reliable prognostic indicators for patients with pituitary adenomas which will make tumor-specific therapy possible, and help to elucidate the poorly understood phenomenon of pituitary tumorigenesis.

Psychology and psychoanalysis in Brazil - From cultural syncretism to the collapse of liberal individualism

This paper focuses first on cultural syncretism, used to characterize Brazilian culture. The other aspect of this socially and racially blended culture is the unfinished assimilation of liberalism in politics and the economy, which defines Brazilian society. The increased assimilation and dissemination of psychology may be linked with these in cultural and social aspects. During the military period (1964-1974) the major expansion in university-level studies in psychology contributed ideologically to the dissemination of psychology throughout Brazilian society. This introduced a type of psychology that was related primarily to clinical practice and developed in opposition to social work practice. This paper examines the ideological bases for this conflict between clinical and social work. Criteria for understanding the cultural dissemination of psychoanalysis are then discussed, and it is argued that cultural incorporation of psychoanalysis involves the development of discourse complexes to reflect particular aspects of Brazilian society. The criteria (a non-totalitarian society and the displacement of a magical and religious interpretation of mental disturbance by psychiatric interpretation) are evaluated in relation to the peculiarities of Brazilian syncretism. The paper argues that cultural syncretism and the incomplete assimilation of liberal ideology must be included as criteria in understanding the particular cultural incorporation of psychoanalysis in Brazil.

Seven new species of Cerambycidae (Coleoptera) from South America with the proposal of three new genera

The following new species are described - Cerambycinae, Sydacini: Sydax flechtmanni sp. nov. from Brazil (São Paulo); Eburiini: Ebrodacrys biffipradorum sp. nov. from Brazil (Roraima); - Lamiinae, Pteropliini: Ataxia piauiensis sp. nov. from Brazil (Piuaí); Calliini: Amucallia carbonaria sp. nov. from French Guiana; A. citrina sp. nov. from Guiana. Also in Lamiinae, two new genera of Onciderini are proposed. Ubytyra gen. nov., type species U. tuberosa sp. nov. from Peru (Junin) e Japi gen. nov., type species J. duartei sp. nov., from Brazil (São Paulo); Ubytyra gen. nov. can be distinguished by the sides of prothorax with long central spine rounded at apex, and this new feature among Onciderini is discussed. Japi gen. nov., is characterized by a fringe of long hairs on the inner side of antennomere III, present only in species from North and Central America, and gender comparison of these species is done and discussed. In Hemilophini, Pseudotacocha gen. nov., type species P. magnifica sp. nov. from Peru (Cuzco), are described. The new genera can be distinguished by eyes well developed, elytra with two carinae and the apices outer with short spine; a comparison with related genera is done.

Characterization of the motor performance in infants with a diagnosis of Cerebral Palsy in process of rehabilitation: the importance of the proactivity of caregivers

Introduction: The progress in technology, associated to the high survival rate in premature newborn infants in neonatal intensive care units, causes an increase in morbidity. Individuals with CP present complex motor alterations, with primary deficits of abnormal muscle tone affecting posture and voluntary movement, alteration of balance and coordination, decrease of force, and loss of selective motor control with secondary problems of contractures and bone deformities. Objective: The aim of this work is to describe the spontaneous movement and strategies that lead infants with cerebral palsy to move. Methods: Seven infants used to receive assistance at the Essential Stimulation Center of CIAM (Israeli Center for Multidisciplinary Support - Philanthropic Institution), with ages ranging between six and 18 months with diagnosis of Cerebral Palsy (CP) were assessed. Results: The results show the difficulty presented by the infants with respect to the spontaneous motor functions and the necessity of help from the caregiver in order to perform the functional activity (mobility). Prematurity prevails as the major risk factor among the complications. Conclusion: The child development can be understood as a product of the dynamic interactions involving the infant, the family, and the context. Thus, the social interactions and family environment in which the infant live may encourage or limit both the acquisition of skills and the functional independence.

Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis

The Na+/H+ exchanger isoform 3 (NHE3) is essential for HCO3- reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO3- concentration in the cell culture medium and respiratory acidosis by increasing CO2 tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 +/- 0.02) and severe (6.95 +/- 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 +/- 0.03) and severe (6.86 +/- 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

Biomarkers of exposure to metal contamination and lipid peroxidation in the benthic fish Cathorops spixii from two estuaries in South America, Brazil

Biomarkers as lipid peroxidation, metallothionein and delta-aminolevulinic acid dehydratase were determined in Cathorops spixii to compare the biological responses of this fish from estuaries with distinct anthropogenic influence. Three areas were selected in two estuaries in accordance with the levels of contamination for the polluted (Santos/So Vicente) and with the hydrodynamic characteristics for the non-polluted (Canan,ia) estuary. Water characteristics and mercury levels in C. spixii confirmed a high human influence in the polluted system. In general, the biomarkers showed differences between the estuaries, suggesting disturbances in the specific cell mechanisms due to the presence of multiple xenobiotics in the contaminated system. Therefore, these biomarkers are recommended to promote more accurate information about the exposure to pollutants. Additionally, the study of the effect of the multiple xenobiotics on resident species such as the benthic fish C. spixii can favor a better assessment of the environmental quality of these systems.

Evolutionary Insights from Bat Trypanosomes: Morphological, Developmental and Phylogenetic Evidence of a New Species, Trypanosoma (Schizotrypanum) erneyi sp nov., in African Bats Closely Related to Trypanosoma (Schizotrypanum) cruzi and Allied Species

Parasites of the genus Trypanosoma are common in bats and those of the subgenus Schizotrypanum are restricted to bats throughout the world, with the exception of Trypanosoma (Schizotrypanum) cruzi that also infects other mammals and is restricted to the American Continent. We have characterized trypanosome isolates from Molossidae bats captured in Mozambique, Africa. Morphology and behaviour in culture, supported by phylogenetic inferences using SSU (small subunit) rRNA, gGAPDH (glycosomal glyceraldehyde 3-phosphate dehydrogenase) and Cyt b (cytochrome b) genes, allowed to classify the isolates as a new Schizotrypanum species named Trypanosoma (Schizotrypanum) erneyi sp. nov. This is the first report of a Schizotrypanum species from African bats cultured, characterized morphologically and biologically, and positioned in phylogenetic trees. The unprecedented finding of a new species of the subgenus Schizotrypanum from Africa that is closest related to the America-restricted Trypanosoma (Schizotrypanum) cruzi marinkellei and T. cruzi provides new insights into the origin and evolutionary history of T. cruzi and closely related bat trypanosomes. Altogether, data from our study support the hypothesis of an ancestor trypanosome parasite of bats evolving to infect other mammals, even humans, and adapted to transmission by triatomine bugs in the evolutionary history of T. cruzi in the New World. (c) 2012 Elsevier GmbH. All rights reserved.