Perinatal lead exposure affects nitric oxide and cyclooxygenase pathways in aorta of weaned rats

Perinatal Pb exposure may modulate arterial tone through nitric oxide (NO) and cyclooxygenase products. To investigate this, Wistar dams received 1000 ppm of Pb or sodium acetate (control) in drinking water during pregnancy and lactation. Curves were constructed in phenylephrine-precontracted intact and/or denuded rings of thoracic aortas of weaned (23-day-old) male pups from their responses to N-omega-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and ACh in the absence or presence of indomethacin (10(-5)M, cyclooxygenase inhibitor) or L-NAME (3 x 10(-7)M and 3 x 10(-4)M). Blood lead concentration and systolic blood pressure (SBP) were higher in intoxicated than control pups (blood lead mu g/dl: control < 3.0, Pb 58.7 +/- 6.5*; SBP mmHg: control 111.4 +/- 2.3, Pb 135.5 +/- 2.4*). In L-NAME-treated rings maximal responses increased in Pb-exposed rats, and were higher in intact than in denuded aortas (contraction [% of phenylephrine] intact: control 184.3 +/- 23.7, Pb 289.1 +/- 18.3*; denuded: control 125.1 +/- 4.5, Pb 154.8 +/- 13.3*). ACh-induced relaxation in intact aortas from Pb-exposed rats presented rightward shift in L-NAME presence (EC50 x 10(-7)M: control 1.32 [0.33-5.18], Pb 4.88 [3.56-6.69]*) but moved left under indomethacin (EC50 x 10(-7)M: control 8.95 [3.47-23.07], Pb 0.97 [0.38-2.43]*). *p < 0.05 significant relative to the respective control; N = 7-9. Endothelium removal abolished ACh-induced relaxation. Perinatal Pb exposure caused hypertension associated with alterations in the production and/or release of basal and stimulated endothelium-derived relaxing factors-NO and constricting cyclooxygenase products. These findings may help explain the contribution of NO and cyclooxygenase products to the etiology and/or maintenance of Pb-induced hypertension and could ultimately lead to therapeutic advantages in plumbism.

B lineage acute lymphoblastic leukemia transformation in a child with juvenile myelomonocytic leukemia, type 1 neurofibromatosis and monosomy of chromosome 7 - Possible implications in the leukemogenesis

This report describes the case of an 8-month-old infant with a diagnosis of juvenile myelomonocytic leukemia (JMML) and type I neurofibromatosis that presented progression to B lineage acute lymphoid leukemia (ALL). The same rearrangement of gene T-cell receptor gamma (TCRgamma) was detected upon diagnosis of JMML and ALL, suggesting that both neoplasias may have evolved from the same clone. Our results support the theory that JMML may derive from pluripotential cells and that the occurrence of monosomy of chromosome 7 within a clone of cells having an aberrant neurofibromatosis type 1 (NFI) gene may be the cause of JMML and acute leukemia. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

Doxazosin Treatment Alters Stromal Cell Behavior and Increases Elastic System Fibers Deposition in Rat Prostate

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The role of nitric oxide in regulation of the cardiovascular system in reptiles

The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and, preliminary data on the effects of SNP inhibition of nitric oxide synthase (NOS) by L-nitroarginine methyl ester (L-NAME). Furthermore. on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from Our laboratory on three other species of reptiles: pythons (Skovgaard, N., Galli, G., Taylor, E.W., Conlon, J.M., Wang.. T., 2005. Hemodynamic effects of python neuropeptide gamma in the anesthetized python, Python regius. Regul. Pept. 18, 15-26), rattlesnakes (Galli, G., Skovgaard, N., Abe, A.S., Taylor, E.W., Wang, T., 2005. The role of nitric oxide in the regulation of the systemic and the pulmonary vasculature of the rattlesnake, Crotalus durissus terrificus. J. Comp. Physiol. 175B, 201-208) and turtles (Crossley, D.A., Wang, T., Altimiras, J., 2000. Role of nitric oxide in the systemic and pulmonary circulation of anesthetized turtles (Trachemys scripta). J. Exp. Zool. 286, 683-689). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies oil reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast., the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity. (C) 2005 Elsevier B.V. All rights reserved.

Autonomic control of cardiorespiratory interactions in fish, amphibians and reptiles

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Autonomic control of heart rate is virtually independent of temperature but seems related to the neuroanatomy of the efferent vagal supply to the heart in the bullfrog, Lithobathes catesbeianus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Processamento auditivo na perda auditiva unilateral: relato de caso

A perda auditiva unilateral representa grande risco para o atraso acadêmico, a comunicação, o desenvolvimento social e também para o processamento auditivo. Assim, o objetivo deste estudo foi avaliar as habilidades auditivas de localização, fechamento, figura-fundo, resolução temporal e ordenação temporal simples de um sujeito do gênero masculino, 17 anos de idade, com diagnóstico de perda auditiva sensorioneural unilateral de grau profundo, de causa idiopática, sem outros comprometimentos. O processo de avaliação constituiu da aplicação de um questionário, da realização da avaliação audiológica clínica convencional (audiometria tonal, logoaudiometria e imitanciometria) e de testes de processamento auditivo monóticos (SSI ipsilateral, Teste de fala filtrada) e dióticos (Localização sonora, Memória auditiva para sons verbais, Memória auditiva para sons não verbais, AFT-R). Apenas o teste de Localização sonora apresentou resultados alterados. Não foram relatadas queixas relacionadas à habilidade de localização sonora, atenção, discriminação e compreensão auditiva. No caso em estudo, a perda auditiva sensorioneural unilateral de grau profundo não pareceu restringir o desenvolvimento das habilidades do processamento auditivo avaliadas, exceto no que se refere à localização da fonte sonora.

Identificação de zonas mortas da cóclea por meio do teste TEN

O audiograma ou o relato do paciente não é suficiente para determinar a presença ou não de zonas mortas na cóclea (ZMC), nem identificar sua extensão. OBJETIVO: Investigar, utilizando o teste TEN, ZMC de indivíduos com perda auditiva neurossensorial (PANS). CEDALVI/ HRAC-USP-Bauru, de agosto de 2003 a fevereiro de 2004. TIPO DE ESTUDO: Estudo de coorte contemporânea com corte transversal. Casuística e Métodos: O TEN foi aplicado nos grupos G1 (5 mulheres com limiares tonais aéreos dentro do padrão de normalidade); G2 (4 mulheres e 5 homens com PANS moderada plana); G3 (19 mulheres e 24 homens com PANS com o grau variando entre leve a profundo). RESULTADOS: Para G1, o valor de TEN para eliminar o tom de teste foi, em média, próximo ao limiar absoluto para todas as freqüências. Não foi observada ZMC em nenhuma das orelhas testadas do G2. Para as 76 orelhas do G3, 6 não apresentaram indício de ZM. CONCLUSÕES: O TEN é efetivo para indicar ZMC em indivíduos com PANS descendente. Há evidência de diferença na detecção do tom puro na presença de ruído entre indivíduos com PANS em altas freqüências e com PANS plana, pois se observou diferença significativa entre o limiar mascarado e absoluto apenas para PANS descendentes e não para as planas.

Chromosomal imbalances detected in primary bone tumors by comparative genomic hybridization and interphase fluorescence in situ hybridization

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lipophyllic antioxidants from Iryanthera juruensis fruits

The phytochemical investigation of the hexane extract of I,:Iryanthera juruensis (Myristicaceae) fruits led to the isolation of two tocotrienols and four lignans which exhibited antioxidant activity towards beta -carotene on TLC autographic assay. Two inactive quinones and three omega -arylalkanoic acids were also isolated. The isolates were investigated for their redox properties using cyclic voltammetry. The structure elucidation of the new compounds tone tocotrienol. one quinone and three w-arylalkanoic acids) was based on analysis of spectroscopic data, (C) 2001 Elsevier B.V. Ltd. All rights reserved.

The Brazilian pediatric myelodysplastic cooperative group strategies: are they relevant to improve educational approach and correct diagnosis?

Brazil is a wide country with huge contrasts. Its peculiarities can highlight environmental factors that could influence the frequencies of different cancers. The standard treatment and results achieved from several different areas of the country may not be found in others. The establishment of a national cooperative group has the potential to improve outcomes. The The Brazilian Cooperative Group on Pediatric Patients with Myelodysplastic Syndrome (BCG-MDS-PED) was first organized in January 1997 as a working group of hematologists, pediatric oncologists, pediatric-hematologists, molecular biologists and other professionals in order to study pediatric (age < 18 years) MDS. Six distinct subcommittees constituted with members from several universities: cytology, histopathology, clinical, cytogenetics, molecular biology and epidemiology. The goals of the BCG-MDS-PED were: (i) to offer support for diagnosis and orientation for treatment; (ii) educational Support for the colleagues all over the country and (iii) research on pathogenesis and new approaches for pediatric MDS patients. There are socio-economical differences among the five regions of the country. The BCG-MDS-PED believes that it is absolutely necessary to Study the clinical, cellular, molecular and epidemiological aspects of MDS, taking in account these peculiar differences among populations and regions. Since 1997, 114 pediatric cases were referred to the BCG-MDS-PED from 21 centres. Seven Brazilian states have sent cases to the group, 31 patients were referred from universities, 73 patients from pediatric oncology units (foundations) and 10 patients came from private clinics. Some of these patients have been followed up and/or treated by the physician who referred them to the BCG-MDS-PED for confirmation of the initial diagnosis. The majority of these physicians have required orientation on diagnostic and treatment issues, as well as to complete cytogenetic and molecular studies. From these 114 patients, 64 patients were confirmed as MDS. We believe that, the more numerous the MDS-studied cases, the more experienced will be the referee group on clinical and laboratory features on childhood MDS in Brazil. (C) 2002 Published by Elsevier B.V. Ltd.

Role of 5-HT in stress, anxiety, and depression

There are conflicting results on the function of 5-HT in anxiety and depression. To reconcile this evidence, Deakin and Graeff have suggested that the ascending 5-HT pathway that originates in the dorsal raphe nucleus (DRN) and innervates the amygdala and frontal cortex facilitates conditioned fear, while the DRN-periventricular pathway innervating the periventricular and periaqueductal gray matter inhibits inborn fight/flight reactions to impending danger, pain, or asphyxia. To study the role of the DRN 5-HT system in anxiety, we microinjected 8-OH-DPAT into the DRN to inhibit 5 HT release. This treatment impaired inhibitory avoidance (conditioned fear) without affecting one-way escape (unconditioned fear) in the elevated T-maze, a new animal model of anxiety. We also applied three drug treatments that increase 5-HT release from DRN terminals: 1) intra-DRN microinjection of the benzodiazepine inverse agonist FG 4172, 2) intra-DRN microinjection of the excitatory amino acid kainic acid, and 3) intraperitoneal injection of the 5-HT releaser and uptake blocker D-fenfluramine. All treatments enhanced inhibitory avoidance in the T-maze. D-Fenfluramine and intra-DRN kainate also decreased one-way escape. In healthy volunteers, D-fenfluramine and the 5-HT agonist mCPP (mainly 5-HT2C) increased, while the antagonists ritanserin (5-HT2A/(2C)) and SR 46349B (5-HT2A) decreased skin conductance responses to an aversively conditioned stimulus (tone). In addition, D-fenfluramine decreased, whereas ritanserin increased subjective anxiety induced by simulated public speaking, thought to represent unconditioned anxiety. Overall, these results are compatible with the above hypothesis. Deakin and Graeff have suggested that the pathway connecting the median raphe nucleus (MRN) to the dorsal hippocampus promotes resistance to chronic, unavoidable stress. In the present study, we found that 24 h after electrolytic lesion of the rat MRN glandular gastric ulcers occurred, and the immune response to the mitogen concanavalin A was depressed. Seven days after the same lesion, the ulcerogenic effect of restraint was enhanced. Microinjection of 8-OH-DPAT, the nonselective agonist 5-MeO-DMT, or the 5-HT uptake inhibitor zimelidine into the dorsal hippocampus immediately after 2 h of restraint reversed the deficits of open arm exploration in the elevated plus-maze, measured 24 h after restraint. The effect of the two last drugs was antagonized by WAY-100135, a selective 5-HT1A receptor antagonist. These results are compatible with the hypothesis that the MRN-dorsal hippocampus 5-HT system attenuates stress by facilitation of hippocampal 5-HT1A-mediated neurotransmission. Clinical implications of these results are discussed, especially with regard to panic disorder and depression.

Vagal control of heart rate and cardiac shunts in reptiles: Relation to metabolic state

The vagus is clearly of primary importance in the regulation of reptilian cardiorespiratory systems. Vagal control of pulmonary blood flow and cardiac shunts provides reptiles with an additional means of regulating arterial oxygen levels that is not present in endothermic vertebrates (birds and mammals). Within a given species, there exists a clear correlation between withdrawal of vagal tone on the cardiovascular system and elevated metabolic rate. Undisturbed and resting reptiles are normally characterised by high vagal tone, low pulmonary blood flow and large right-left (R-L) cardiac shunts. The low oxygen levels that result from the large R-L shunt may serve to regulate metabolism. However, when metabolism is increased by temperature, exercise or digestion, the R-L cardiac shunt is reduced, which serves to increase oxygen delivery. This response is partially elicit ed by reduction of vagal tone. Interspecies comparisons reveal a similar pattern. Thus, species that are able to sustain the highest metabolic rates possess the highest degree of anatomical ventricular separation and, therefore, less cardiac shunting. It is interesting to note that when cardiac shunts occur in mammals, due for example to developmental defects, they are associated with reduced maximal metabolic rates and impaired exercise tolerance. It appears, therefore, that full separation of ventricular blood flows was a prerequisite for the evolution of high aerobic metabolic rates and exercise stamina in mammals and birds.

Sino-aortic denervation causes right atrial beta adrenoceptor down-regulation

Rat isolated right atria obtained 1 wk after sinoaortic denervation were less sensitive to the chronotropic actions of beta-agonists than were tissues obtained from animals that underwent sham surgery or no surgery at all. The potencies, but not the maximal responses for two high efficacy agonists, norepinephrine and isoproterenol, were reduced about 3- to 4-fold. Sinoaortic denervation (SAD) caused about a 3-fold decrease in potency and about a 60% decrease in maximal response for a low efficacy agonist, prenalterol. The changes in the actions of these agonists occurred in the absence of any changes in the subtype of beta receptor mediating the chronotropic response. The results of analyses of the data for prenalterol showed that SAD caused a decrease in the operational efficacy of this agonist without any changes in its K-D value for beta-1 adrenoceptors. SAD had no effect on the responses of the tissue to blockade of uptake 1 and uptake 2, suggesting no compensatory changes in the removal processes caused the decreased potency. The results of radioligand binding assays showed that SAD caused a decrease in the maximal binding of I-125-cyanopindolol without altering its K-D. Also, the results of competition binding assays confirmed the lack of effect of SAD on the K-D for prenalterol. The SAD-induced changes in the actions of agonists acting at right atrial beta-1 receptors were caused by a down-regulation of beta-1 adrenoceptors, which probably occurred in response to SAD-induced increases in sympathetic tone.