Peripheral withdrawal recruits distinct central nuclei in morphine-dependent rats

This study examined if brain pathways in morphine-dependent rats are activated by opioid withdrawal precipitated outside the central nervous system. Withdrawal precipitated with a peripherally acting quaternary opioid antagonist (naloxone methiodide) increased Fos expression but caused a more restricted pattern of neuronal activation than systemic withdrawal (precipitated with naloxone which enters the brain). There was no effect on locus coeruleus and significantly smaller increases in Fos neurons were produced in most other areas. However in the ventrolateral medulla (A1/C1 catecholamine neurons), nucleus of the solitary tract (A2/C2 catecholamine neurons), lateral parabrachial nucleus, supramamillary nucleus, bed nucleus of the stria terminalis. accumbens core and medial prefrontal cortex no differences in the withdrawal treatments were detected. We have shown that peripheral opioid withdrawal can affect central nervous system pathways. Crown Copyright (C) 2001 Published by Elsevier Science Ltd. All rights reserved.

Comparison of pulmonary vascular function and structure in early and established hypoxic pulmonary hypertension in rats

In pulmonary hypertension, changes in pulmonary vascular structure and function contribute to the elevation in pulmonary artery pressure. The time-courses for changes in function, unlike structure, are not well characterised. Medial hypertrophy and neomuscularisation and reactivity to vasoactive agents were examined in parallel in main and intralobar pulmonary arteries and salt-perfused lungs from rats exposed to hypoxia (10% O-2) for 1 and 4 weeks (early and established pulmonary hypertension, respectively). After 1 week of hypoxia, in isolated main and intralobar arteries, contractions to 5-hydroxytryptamine and U46619 (thromboxane-mimetic) were increased whereas contractions to angiotensins I and II and relaxations to acetylcholine were reduced. These alterations varied quantitatively between main and intralobar arteries and, in many instances, regressed between 1 and 4 weeks. The alterations in reactivity did not necessarily link chronologically with alterations in structure. In perfused lungs, constrictor responses to acute alveolar hypoxia were unchanged after 1 week but were increased after 4 weeks, in conjunction with the neomuscularisation of distal alveolar arteries. The data suggest that in hypoxic pulmonary hypertension, the contribution of altered pulmonary vascular reactivity to the increase in pulmonary artery pressure may be particularly important in the early stages of the disease.

Pulmonary Vascular remodelling in hypoxic rats: effects of amlodipine, alone and with perindopril

This study investigated whether pulmonary Vascular remodelling in hypoxic pulmonary hypertensive rats (10% oxygen; 4 weeks) could be prevented by treatment, during hypoxia, with amlodipine (IO mg/kg/day, p.o.), either alone or in combination with the angiotensin converting enzyme inhibitor, perindopril (30 mg/kg/day, p.o.). Medial thickening of pulmonary arteries (30-500 mum o.d.) was attenuated by amlodipine whereas it was totally prevented by the combination treatment (amlodipine plus perindopril); neomuscularisation of small alveolar arteries (assessed from critical closing pressure in isolated perfused lungs) was not affected. Pulmonary vascular resistance (isolated perfused lungs) was reduced by both treatment regimes but only combination treatment reduced right ventricular hypertrophy. Taus, amlodipine has anti-remodelling properties in pulmonary hypertensive rats. The finding that combining amlodipine with another anti-remodelling drug produced effects on vascular structure that were additive raises the question of whether combination therapy with two different anti-remodelling drugs may be of value in the treatment of patients with hypoxic (and possibly other forms of) pulmonary hypertension. (C) 2001 Elsevier Science B.V. All rights reserved.

An architectonic comparison of the ventrobasal complex of two Megachiropteran and one Microchiropteran bat: implications for the evolution of Chiroptera

The architectonic features of the thalamic ventrobasal complex (Vb) of two species of Megachiropteran (Grey-headed flying fox, Pteropus poliocephalus, and the Eastern tube-nosed bat, Nyctimene robinsoni) are compared with those of a Microchiropteran (Australian ghost bat, Macroderma gigas). The somatosensory system was chosen for comparison as it represents a sensory system that has undergone analogous modifications in both Chiropteran lineages (the evolution of the wing). The components of Vb were examined as there are taxon-specific features in this region of the brain. Within the Megachiropteran Vb, four subnuclei were recognized: the ventral posterior medial (VPM), the ventral posterior lateral (VPL), the ventral posterior inferior (VPI), and the basal ventral medial (VMb). In the ghost bat only VPM and VPL were identified with certainty. No VPI was evident in the ghost bat, however a putative VMb was observed. Vb of the ghost bat also lacked the arcuate lamina, which distinguishes VPM from VPL in the Megachiropterans and many other mammals. These taxon-specific differences lend support to the proposal that the order Chiroptera has a diphyletic origin.

Relationship of glycosaminoglycan and matrix changes to vascular smooth cell phenotype modulation in rabbit arteries after acute injury

Purpose: The phenotype of vascular smooth muscle cells (SMCs) is altered in several arterial pathologies, including the neointima formed after acute arterial injury. This study examined the time course of this phenotypic change in relation to changes in the amount and distribution of matrix glycosaminoglycans. Methods: The immunochemical staining of heparan sulphates (HS) and chondroitin sulphates (CS) in the extracellular matrix of the arterial wall was examined at early points after balloon catheter injury of the rabbit carotid artery. SMC phenotype was assessed by means of ultrastructural morphometry of the cytoplasmic volume fraction of myofilaments. The proportions of cell and matrix components in the media were analyzed with similar morphometric techniques. Results: HS and CS were shown in close association with SMCs of the uninjured arterial media as well as being more widespread within the matrix. Within 6 hours after arterial injury, there was loss of the regular pericellular distribution of both HS and CS, which was associated with a significant expansion in the extracellular space. This preceded the change in ultrastructural phenotype of the SMCs. The glycosaminoglycan loss was most exaggerated at 4 days, after which time the HS and CS reappeared around the medial SMCs. SMCs of the recovering media were able to rapidly replace their glycosaminoglycans, whereas SMCs of the developing neointima failed to produce HS as readily as they produced CS. Conclusions: These studies indicate that changes in glycosaminoglycans of the extracellular matrix precede changes in SMC phenotype after acute arterial injury. In the recovering arterial media, SMCs replace their matrix glycosaminoglycans rapidly, whereas the newly established neointima fails to produce similar amounts of heparan sulphates.

Nitric oxide, a potent vasodilator of the aortic anastomosis in the estuarine crocodile, Crocodylus porosus

The effects of five neuropeptides (CGRP, SOM, SP, NPY, VIP), L-NAME (nitric oxide synthase inhibitor), and adrenaline on the contractile tone of the aortic anastomosis in the estuarine crocodile, Crocodylus porosus, were investigated. None of the neuropeptides, which had previously been found to be present in the aortic anastomosis, had any direct effect on the tension developed by ring preparations. L-NAME itself significantly increased the basal tone of the vascular ring preparations, suggesting a tonic release of nitric oxide in the preparation. Adrenaline produced concentration-dependent vasoconstrictions that were counteracted by profound reflex vasodilatations that were susceptible to blockade by L-NAME. Immunohistochemistry revealed the presence of nitric oxide synthase and tyrosine hydroxylase-containing (indicating the presence of a adrenergic innervation) nerve fibres in the adventitia and adventitio-medial border of the aortic anastomosis. These data demonstrate opposing actions of adrenaline and nitric oxide on the vascular smooth muscle in the anastomosis of the C. porosus. The morphology of the anastomosis, with the extremely thick muscular vessel wall, suggests a sphincter-like function for this vessel that could be controlled mainly by adrenergic and nitrergic mechanisms, (C) 2001 Academic Press.

Brain activity during the encoding, retention, and retrieval of stimulus representations

Studies of delayed nonmatching-to-sample (DNMS) performance following lesions of the monkey cortex have revealed a critical circuit of brain regions involved in forming memories and retaining and retrieving stimulus representations. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activity in 10 healthy human participants during performance of a trial-unique visual DNMS task using novel barcode stimuli. The event-related design enabled the identification of activity during the different phases of the task (encoding, retention, and retrieval). Several brain regions identified by monkey studies as being important for successful DNMS performance showed selective activity during the different phases, including the mediodorsal thalamic nucleus (encoding), ventrolateral prefrontal cortex (retention), and perirhinal cortex (retrieval). Regions showing sustained activity within trials included the ventromedial and dorsal prefrontal cortices and occipital cortex. The present study shows the utility of investigating performance on tasks derived from animal models to assist in the identification of brain regions involved in human recognition memory.

Macrophages, myofibroblasts and neointimal hyperplasia after coronary artery injury and repair

Macrophages participate in the restenosis process through the release of cytokines, metalloproteinases and growth factors. Studies of peritoneal granulation tissue suggest that macrophages may be precursors of myofibroblasts. This study examined the contribution of monocyte/macrophage lineage cells to neointimal cellular mass in a porcine model of thermal vascular injury. Thermal coronary artery injury caused medial smooth muscle cell necrosis and transformation of the media into an extracellular matrix barrier. The neointimal hyperplasia that developed over the injury sites was evaluated by light microscopy, electron microscopy and immunohistochemistry. At day 3, blood monocytes were adhered to the vessel wall and infiltrated the fibrotic media. At day 14, 42 +/- 3.9% of neointimal cells had a monocytic nuclear morphology and expressed macrophage-specific antigen SWC3 (identified by monoclonal antibody DH59B). Moreover, 9.2+/-1.8% of neointimal cells co-expressed SWC3 and alpha-smooth muscle actin and had ultrastructural characteristics intermediate between macrophages and myofibroblasts. At day 28, 10.5 +/- 3.5%, of cells expressed SWC3 and 5.2+/-1.8% of cells co-expressed SWC3 and alpha-smooth muscle actin. This study indicates that hematopoietic cells of monocyte/macrophage lineage abundantly populate the neointima in the process of lesion formation and may be precursors of neointimal myofibroblasts after thermal vascular injury. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Systemic administration of interleukin-1 beta activates select populations of central amygdala afferents

The central nucleus of the amygdala (CeA) is activated robustly by an immune challenge such as the systemic administration of the proinflammatory cytokine interleukin-1beta (IL-1beta). Because IL-1beta is not believed to cross the blood-brain barrier in any significant amount, it is likely that IL-1beta elicits CeA cell recruitment by means of activation of afferents to the CeA. However, although many studies have investigated the origins of afferent inputs to the CeA, we do not know which of these also respond to IL-1beta. Therefore, to identify candidate neurons responsible for the recruitment of CeA cells by an immune challenge, we iontophoretically deposited a retrograde tracer, cholera toxin b-subunit (CTb), into the CeA of rats 7 days before systemic delivery of IL-1beta (1 mug/kg, i.a.). By using combined immunohistochemistry, we then quantified the number of Fos-positive CTb cells in six major regions known to innervate the CeA. These included the medial prefrontal cortex, paraventricular thalamus (PVT), ventral tegmental area, parabrachial nucleus (PB), nucleus tractus solitarius, and ventrolateral medulla. Our results show that after deposit of CTb into the CeA, the majority of double-labeled cells were located in the PB and the PVT, suggesting that CeA cell activation by systemic IL-1beta is likely to arise predominantly from cell bodies located in these regions. These findings may have significant implications in determining the central pathways involved in generating acute central responses to a systemic immune challenge. J. Comp. Neurol. 452:288-296, 2002. (C) 2002 Wiley-Liss, Inc.

Abnormal extracellular matrix protein transport associated with increased apoptosis of vascular smooth muscle cells in Marfan syndrome and bicuspid aortic valve thoracic aortic aneurysm

Background - Marfan syndrome (MS) is a genetic disorder caused by a mutation in the fibrillin gene FBN1. Bicuspid aortic valve (BAV) is a congenital heart malformation of unknown cause. Both conditions are associated with ascending aortic aneurysm and premature death. This study examined the relationship among the secretion of extracellular matrix proteins fibrillin, fibronectin, tenascin, and vascular smooth muscle cell (VSMC) apoptosis. The role of matrix metalloproteinase (MMP)- 2 in VSMC apoptosis was studied in MS aneurysm. Methods and Results - Aneurysm tissue was obtained from patients undergoing surgery ( MS: 4 M, 1 F, age 27 - 45 years; BAV: 3 M, 2 F, age 28 - 65 years). Normal aorta from subjects with nonaneurysm disease was also collected ( 4 M, 1 F, age 23 - 93 years). MS and BAV aneurysm histology showed areas of cystic medial necrosis (CMN) without inflammatory infiltrate. Immunohistochemical study of cultured MS and BAV VSMC showed intracellular accumulation and reduction of extracellular distribution of fibrillin, fibronectin, and tenascin. Western blot showed no increase in expression of fibrillin, fibronectin, or tenascin in MS or BAV VSMC and increased expression of MMP-2 in MS VSMCs. There was 4-fold increase in loss of cultured VSMC incubated in serum-free medium for 24 hours in both MS ( 27 +/- 8%) and BAV ( 32 +/- 14%) compared with control ( 7 +/- 5%). Conclusions - In MS and BAV there is alteration in both the amount and quality of secreted proteins and an increased degree of VSMC apoptosis. Up-regulation of MMP-2 might play a role in VSMC apoptosis in MS VSMC. The findings suggest the presence of a fundamental cellular abnormality in BAV thoracic aorta, possibly of genetic origin.

Análise do padrão de ativação muscular de indivíduos hemiparéticos pós-AVC em marcha assistida por andador robótico

O Acidente Vascular Cerebral (AVC) é uma das principais causas de prejuízos ao sistema neuromuscular. Dispositivos Robóticos vêm sendo amplamente desenvolvidos e estudados com a finalidade de serem utilizados na assistência à marcha e para o treinamento da marcha durante a reabilitação. O objetivo deste trabalho é avaliar a marcha assistida pelo AROW (Assistive Robotic Walker) em indivíduos hemiparéticos pós-AVC, através da análise de sinais de acelerometria e sinais mioelétricos de superfície (sEMG) provenientes dos músculos vasto medial (VM), bíceps femoral (BF), tibial anterior (TA) e gastrocnêmio medial (GM), e também utilizando os métodos de avaliação GAS (Goal Attainment Scaling) e SUS (System Usability Scale). Nove indivíduos hemiparéticos participaram dos testes. A velocidade da marcha foi reduzida com o uso do AROW e, consequentemente, houve algumas alterações na duração das fases da marcha, por exemplo, uma maior duração da fase de apoio (p = 0,0174). O padrão de ativação muscular para o grupo analisado não apresentou diferença estatisticamente significativa (início da ativação VM: p= 0,4999; término da ativação VM: p= 0,5647; início BF: p= 0,1186; término BF: p= 0,7823; início TA: p= 0,5833; término TA: p= 0,8393; início GM: p= 0,6077; término GM: p= 0,1429). Entretanto, avaliando o padrão de ativação muscular individualmente, podem-se notar algumas alterações benéficas, por exemplo, redução da coativação dos músculos tibial anterior e gastrocnêmio medial. Os resultados das avaliações através do GAS (54,8) e SUS (81,4) sobre o uso do AROW mostraram boa aceitação pelos usuários, e os objetivos esperados durante o uso do andador foram atingidos. A adaptação rápida, facilidade de utilização e sentimento de segurança ao usar o dispositivo são pontos positivos obtidos com o uso do AROW.

Complicações rinossinusais após descompressão orbital em técnica externa e endonasal combinada

Muitas técnicas de descompressão orbital têm sido utilizadas no tratamento da oftalmopatia por Graves. Recentemente, introduziu-se a cirurgia endoscópica endonasal na descompressão de órbita, como técnica isolada ou combinada com as já existentes, acreditando proporcionar melhor visão da parede medial da órbita e menor incidência de infecção bacteriana quando a parede medial é acessada por endoscópio. OBJETIVO: Avaliar as complicações após a descompressão orbital por técnica combinada assistida por endoscopia na prevenção de infecção rinossinusal. FORMA DE ESTUDO: Clínico Prospectivo. MATERIAL E MÉTODO: 16 pacientes 18 órbitas foram submetidos à descompressão orbital no Setor de Órbita do Departamento de Oftalmologia da Escola Paulista de Medicina UNIFESP. RESULTADOS: Quatro pacientes, durante o acompanhamento por tomografia no pós-operatório, apresentaram velamento do seio maxilar ou frontal, sem sintomatologia. CONCLUSÃO: A descompressão orbital por via externa combinada com a via endonasal auxiliada por endoscopia mostrou-se eficaz na prevenção de sinusite clinicamente manifesta e suas complicações, embora no acompanhamento tomográfico 22% dos pacientes apresentaram velamento do seio maxilar ou frontal.

Cervicoplastia anterior

Muitos pacientes buscam correção estética da frouxidão da pele do pescoço, depósito de gordura na região submentoneana ou bandas de platisma. Em grande parte dos casos a ação medial, via cervicoplastia anterior é necessária. OBJETIVO: Demonstrar a casuística e avaliar os resultados e complicações com a técnica de cervicoplastia anterior no Serviço de Otorrinolaringologia da Universidade Federal de Uberlândia. FORMA DE ESTUDO: Relato de série. PACIENTES E MÉTODOS: Quarenta e dois pacientes, entre 39 e 65 anos de idade, sendo 40 (95,2%) do sexo feminino e 2 (4,8%) do masculino, foram submetidos a cervicoplastia anterior. Retrospectivamente foram avaliados resultados e complicações. RESULTADOS: Destes, 34 apresentaram resultados satisfatórios, 4 apresentaram déficit estético notado somente pelo cirurgião, 3 apresentaram déficit estético notado somente pelo paciente e 1 apresentou déficit estético necessitando cirurgia revisional. Ao estudo fotográfico, todos os pacientes apresentaram melhora do perfil cervical, redução das bandas de platisma e da frouxidão da pele, estabilização da musculatura cervical e acentuação do ângulo cervicomental, em graus variados. Houve complicação em 2 casos (discreto serohematoma e cicatriz um pouco alargada). CONCLUSÃO: A cervicoplastia, associada ou não à tração lateral pela ritidoplastia, é uma técnica que produz resultados satisfatórios na grande maioria dos casos.

Resultados auditivos com o implante coclear multicanal em pacientes submetidos a cirurgia no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

A surdez profunda é uma deficiência que afeta a personalidade, o relacionamento e todo o estilo de vida do paciente. Incapacita os indivíduos de escutarem sons ambientes como sirenes e alarmes que constituem alerta em situações da vida diária e não permite a modulação vocal, tornando a voz esteticamente ruim. A prótese auditiva convencional é eficiente no tratamento de grande parte das deficiências auditivas, porém existem pacientes que não conseguem obter discriminação de palavras e sentenças mesmo com uma prótese auditiva potente. O implante coclear é a alternativa atual para estes pacientes. OBJETIVO: Avaliar o resultado auditivo dos pacientes adultos implantados com o implante coclear multicanal pelo Grupo de Implante Coclear da Disciplina de Otorrinolaringologia da Faculdade de medicina da Universidade de São Paulo. FORMA DE ESTUDO: Estudo de série. CASUÍSTICA E MÉTODO: Foram selecionados 61 pacientes com surdez profunda bilateral que utilizam o implante coclear multicanal por pelo menos seis meses e estudados os resultados auditivos através de testes de reconhecimento de palavras e sentenças. RESULTADOS: O PTA médio obtido pelos pacientes foi 38.7 dB NPS. A média em reconhecimento de sentenças em formato aberto foi de 71.3%, vogais em 86.5%, monossílabos em 52.60% e consoante medial em 52.6%. A maioria dos pacientes está apta ao uso do telefone. CONCLUSÃO: A avaliação auditiva obtida seis meses após a primeira programação do implante demonstra que pacientes de língua portuguesa obtêm excelentes resultados em testes de reconhecimento de palavras e sentenças em apresentação aberta, readquirindo uma audição útil.

Configuração das pregas vestibulares à fonação em adultos com e sem disfonia

As pregas vestibulares participam da emissão vocal com mudanças evidentes de posição e forma durante este processo, porém pouco ou quase nada se conhece sobre o significado desta participação e como se iniciam estes movimentos ativos que mudam sua forma e contorno. Entendemos que o conhecimento da participação das pregas vestibulares na fisiologia laríngea possa ter importante aplicação prática, pois permitirá avaliar melhor o comprometimento funcional em condições patológicas, o que auxiliará na definição de estratégias para o adequado tratamento. OBJETIVO: Estudar a configuração da prega vestibular durante a fonação (emissão sustentada do /µ/) comparando exames de indivíduos sem queixa vocal (grupo eufonia) com portadores de queixa de voz (grupo disfonia). FORMA DE ESTUDO: Coorte transversal simples. MATERIAL E MÉTODO: Foram analisados 120 registros de imagens de laringes, sendo 60 de indivíduos eufônicos e 60 de disfônicos, constituído cada grupo de igual número de indivíduos em relação ao gênero. Foi identificada a posição da borda livre de prega vestibular em relação a uma reta que une as inserções anterior e posterior da mesma. Na dependência desta posição, foram descritos três tipos de configurações: côncava, quando estava em posição lateral, convexa quando em posição medial e linear quando paralela ou se sobrepunha. RESULTADOS: Das 240 pregas vestibulares, 158 eram côncavas, 41 convexas e 31 lineares. A forma côncava predominou nos dois grupos em relação às outras, porém as formas convexa e linear aumentaram no grupo disfonia. No feminino, a forma linear teve aumento significante no grupo disfonia, enquanto no masculino o aumento significante ocorreu na forma convexa. CONCLUSÃO: Existe diferença no comportamento da prega vestibular no grupo disfonia em relação à eufonia, sendo que esta diferença ocorre de forma diversa em relação aos gêneros.