963 resultados para Mild, Krister: Pipits
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Journal of Biological Inorganic Chemistry (2010)15: 271-281
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RESUMO: A sndrome de apneia hipopneia obstrutiva do sono (SAHOS), pela sua prevalncia e consequncias clnicas, nomeadamente as de natureza cardiovascular, actualmente considerada um problema de sade pblica. A patognese da doena cardiovascular na SAHOS no est ainda completamente estabelecida, mas parece ser multifactorial, envolvendo diversos mecanismos que incluem a hiperactividade do sistema nervoso simptico, a disfuno endotelial, a activao selectiva de vias inflamatrias, o stress oxidativo vascular e a disfuno metablica. A teraputica com CPAP diminui grandemente o risco de eventos cardiovasculares fatais e no fatais. O CPAP est inequivocamente indicado para o tratamento da SAHOS grave, no entanto, no consensual a sua utilizao nos doentes com SAHOS ligeira/moderada sem hipersonolncia diurna associada. Tendo em conta este facto, fundamental que as indicaes teraputicas do CPAP nestes doentes tenham uma relao custo-eficcia favorvel. Assim, dado o posicionamento do estado da arte relativamente ao estudo da disfuno endotelial e da activao do sistema nervoso simptico estar centrada maioritariamente nos doentes com SAHOS grave, desenvolvemos este estudo com o objectivo de comparar os nveis plasmticos de nitratos, os nveis de catecolaminas urinrias e os valores de presso arterial nos doentes com SAHOS ligeira/moderada e grave e avaliar a resposta destes parmetros ao tratamento com CPAP durante um ms. Realizmos um estudo prospectivo, incidindo sobre uma populao de 67 doentes do sexo masculino com o diagnstico de SAHOS (36 com SAHOS ligeira/moderada e 31com SAHOS grave). O protocolo consistia em 3 visitas: antes da teraputica com CPAP (visita 1), uma semana aps CPAP (visita 2) e um ms aps CPAP (visita 3). Nas visitas 1 e 3, eram submetidos a trs colheitas de sangue s 11 pm, 4 am e 7 am para doseamento dos nitratos plasmticos e na visita 2 apenas s 7 am. Nas visitas 1 e 3 era tambm efectuada uma colheita de urina de 24 horas para o doseamento das catecolaminas urinrias e eram submetidos a uma monitorizao ambulatria da presso arterial de 24 horas (MAPA). Foi ainda estudado um grupo controlo de 30 indivduos do sexo masculino no fumadores sem patologia conhecida e sem evidncia de SAHOS. Antes da teraputica com CPAP, verificou-se uma diminuio significativa dos nveis de nitratos ao longo da noite quer nos doentes com SAHOS ligeira/moderada, quer nos doentes com SAHOS grave. No entanto, esta reduo diferia nos 2 grupos de doentes, sendo significativamente superior nos doentes com SAHOS grave (27,620,1% vs 16,518,5%; p<0,05). Aps um ms de tratamento com CPAP, verificou-se um aumento significativo dos valores de nitratos plasmticos apenas nos doentes com SAHOS grave, mantendo-se os nveis de nitratos elevados ao longo da noite, j no existindo o decrscimo desses valores ao longo da mesma. Os valores de noradrenalina basais eram significativamente superiores nos doentes com SAHOS grave comparativamente com os doentes com SAHOS ligeira/moderada (73,930,1g/24h vs 48,519,91g/24h; p<0,05). Aps um ms de teraputica com CPAP, apenas se verificou uma reduo significativa nos valores da noradrenalina nos doentes com SAHOS grave (73,930,1g/24h para 55,421,8 g/24h; p<0,05). Os doentes com SAHOS grave apresentaram valores de presso arterial mais elevados do que os doentes com SAHOS ligeira/moderada, nomeadamente no que diz respeito aos valores de presso arterial mdia, sistlica mdia de 24 horas, diurna e nocturna e diastlica mdia de 24 horas, diurna e nocturna. Aps um ms de teraputica com CPAP, verificou-se uma reduo significativa dos valores tensionais apenas nos doentescom SAHOS grave, para a presso mdia (-2,32+5,0; p=0,005), para a sistlica mdia de 24 horas (-4,0+7,9mmHg; p=0,009), para a presso sistlica diurna (-4,3+8,8mmHg; p=0,01), para a presso sistlica nocturna (-5,1+9,0mmHg; p=0,005), para a presso diastlica mdia de 24 horas (-2,7+5,8mmHg; p=0,016), para a presso diastlica diurna (-3,2+6,3mmHg; p=0,009) e para a presso diastlica nocturna (-2,5+7,0mmHg; p=0,04). Os nveis tensionais dos doentes com SAHOS grave aps CPAP atingiram valores semelhantes aos dos doentes com SAHOS ligeira/moderada, relativamente a todos os parmetros avaliados no MAPA. Este estudo demonstrou que antes do tratamento com CPAP, existe uma reduo dos nveis de nitratos ao longo da noite no s nos doentes com SAHOS grave mas tambm nos doentes com SAHOS ligeira/moderada. No entanto, a teraputica com CPAP leva a um aumento significativo dos valores de nitratos plasmticos apenas nos doentes com SAHOS grave, mantendo-se os nveis de nitratos elevados ao longo da noite, j no existindo o decrscimo desses valores ao longo da mesma. O tratamento com CPAP durante um ms, apenas reduz os nveis de noradrenalina urinria e os valores de presso arterial nos doentes com SAHOS grave.------------ ABSTRACT: In severe obstructive sleep apnea (OSA) reduced circulating nitrate, increased levels of urinary norepinephrine (U-NE) and changes in systemic blood pressure (BP) have been described and are reverted by Continuous Positive Airway Pressure (CPAP). However, the consequences of mild/moderate OSA on these parameters and the CPAP effect upon them are not well known. We aimed to: 1) compare the levels of plasma nitrate (NOx) and U-NE of mild/moderate and severe male OSA patients 2) compare BP in these patient groups; and 3) determine whether CPAP improves sympathetic dysfunction, nitrate deficiency and BP in these patients. This prospective study was carried out in 67 consecutive OSA patients (36 mild/moderate and 31 severe patients) and NOx (11 pm, 4 am, 7 am), 24-h U-NE and ambulatory blood pressure monitoring were obtained before and after 4 weeks of CPAP. Baseline: NOx levels showed a significant decrease (p<0.001) during the night in both groups of patients. The U-NE and BP were significantly higher in the severe group. Post CPAP: After one month of CPAP, there was a significant increase of NOx, a reduction of U-NE and BP only in severe patients. This study shows that in contrast to severe OSA patients, those with mild/moderate OSA, which have lower values of BP and U-NE at baseline, do not benefit from a 4 weeks CPAP treatment as measured by plasma nitrate, 24-h U-NE levels and BP.
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ABSTRACT: Carotid bodies (CB) are peripheral chemoreceptor organs sensing changes in arterial blood O2, CO2 and pH levels. Hypoxia and acidosis or hypercapnia activates CB chemoreceptor cells, which respond by releasing neurotransmitters in order to increase the action potential frequency in their sensory nerve, the carotid sinus nerve (CSN). CSN activity is integrated in the brainstem to induce a fan of cardiorespiratory reflex responses, aimed at normalising the altered blood gases. Exogenously applied adenosine (Ado) increases CSN chemosensory activity inducing hyperventilation through activation of A2 receptors. The importance of the effects of adenosine in chemoreception was reinforced by data obtained in humans, in which the intravenous infusion of Ado causes hyperventilation and dyspnoea, an effect that has been attributed to the activation of CB because Ado does not cross blood-brain barrier and because the ventilatory effects are higher the closer to the CB it is injected. The present work was performed in order to establish the functional significance of adenosine in chemoreception at the carotid body in control and chronically hypoxic rats. To achieve this objective we investigated: 1) The release of adenosine from a rat carotid body in vitro preparation in response to moderate hypoxia and the specificity of this release. We also investigated the metabolic pathways of adenosine production and release in the organ in normoxia and hypoxia; 2) The modulation of adenosine/ATP release from rat carotid body chemoreceptor cells by nicotinic ACh receptors; 3) The effects of caffeine on peripheral control of breathing and the identity of the adenosine receptors involved in adenosine and caffeine effects on carotid body chemoreceptors; 4) The interactions between dopamine D2 receptors and adenosine A2B receptors that modulate the release of catecholamines (CA) from the rat carotid body; 5) The effect of chronic caffeine intake i.e. the continuous blockage of adenosine receptors thereby simulating a caffeine dependence, on the carotid body function in control and chronically hypoxic rats. The methodologies used in this work included: molecular biology techniques (e.g. immunocytochemistry and western-blot), biochemical techniques (e.g. neurotransmitter quantification by HPLC, bioluminescence and radioisotopic methods), electrophysiological techniques (e.g. action potential recordings) and ventilatory recordings using whole-body plethysmography. It was observed that: 1) CB chemoreceptor sensitivity to hypoxia could be related to its low threshold for the release of adenosine because moderate acute hypoxia (10% O2) increased adenosine concentrations released from the CB by 44% but was not a strong enough stimulus to evoke adenosine release from superior cervical ganglia and arterial tissue; 2) Acetylcholine (ACh) modulates the release of adenosine/5-adenosine triphosphate (ATP) from CB in moderate hypoxia through the activation of nicotinic receptors with 4 and 2 receptor subunits, suggesting that the excitatory role of ACh in chemosensory activity includes indirect activation of purinergic receptors by adenosine and ATP, which strongly supports the hypothesis that ATP/adenosine are important mediators in chemotransduction; 3) adenosine increases the release of CA from rat CB chemoreceptor cells via A2B receptors; 4) the inhibitory effects of caffeine on CB chemoreceptors are mediated by antagonism of postsynaptic A2A and presynaptic A2B adenosine receptors indicating that chemosensory activity elicited by hypoxia is controlled by adenosine; 5) The release of CA from rat CB chemoreceptor cells is modulated by adenosine through an antagonistic interaction between A2B and D2 receptors, for the first time herein described; 6) chronic caffeine treatment did not significantly alter the basal function of CB in normoxic rats assessed as the dynamics of their neurotransmitters, dopamine, ATP and adenosine, and the CSN chemosensory activity. In contrast, the responses to hypoxia in these animals were facilitated by chronic caffeine intake because it increased the ventilatory response, slightly increased CSN chemosensory activity and increased dopamine (DA) and ATP release; 7) In comparison with normoxic rats, chronically hypoxic rats exhibited an increase in several parameters: ventilatory hypoxic response; basal and hypoxic CSN activity; tyrosine hydroxylase expression, CA content, synthesis and release; basal and hypoxic adenosine release; and in contrast a normal basal release and diminished hypoxia-induced ATP release; 8) Finally, in contrast to chronically hypoxic rats, chronic caffeine treatment did not alter the basal CSN chemosensory activity. Nevertheless, the responses to mild and intense hypoxia, and hypercapnia, were diminished. This inhibitory effect of chronic caffeine in CB output is compensated by central mechanisms, as the minute ventilation parameter in basal conditions and in response to acute hypoxic challenges remained unaltered in rats exposed to chronic hypoxia. We can conclude that adenosine both in acute and chronically hypoxic conditions have an excitatory role in the CB chemosensory activity, acting directly on adenosine A2A receptors present postsynaptically in CSN, and acting presynaptically via A2B receptors controlling the release of dopamine in chemoreceptor cells. We suggest that A2B -D2 adenosine / dopamine interactions at the CB could explain the increase in CA metabolism caused by chronic ingestion of caffeine during chronic hypoxia. It was also concluded that adenosine facilitates CB sensitisation to chronic hypoxia although this effect is further compensated at the central nervous system.-------- RESUMO: Os corpos carotdeos (CB) so pequenos orgos emparelhados localizados na bifurcao da artria cartida comum. Estes rgos so sensveis a variaes na PaO2, PaCO2, pH e temperatura sendo responsveis pela hiperventilao que ocorre em resposta hipxia, contribuindo tambm para a hiperventilao que acompanha a acidose metablica e respiratria. As clulas quimiorreceptoras (tipo I ou glmicas) do corpo carotdeo respondem s variaes de gases arteriais libertando neurotransmissores que activam as terminaes sensitivas do nervo do seio carotdeo (CSN) conduzindo a informao ao centro respiratrio central. Est ainda por esclarecer qual o neurotransmissor (ou os neurotransmissores) responsvel pela sinalizao hipxica no corpo carotdeo. A adenosina um neurotransmissor excitatrio no CB que aumenta a actividade elctrica do CSN induzindo a hiperventilao atravs da activao de receptores A2. A importncia destes efeitos da adenosina na quimiorrecepo, descritos em ratos e gatos, foi reforada por resultados obtidos em voluntrios saudveis onde a infuso intravenosa de adenosina em induz hiperventilao e dispneia, efeito atribudo a uma activao do CB uma vez que a adenosina no atravessa a barreira hemato-enceflica e o efeito quanto maior quanto mais perto do CB for a administrao de adenosina. O presente trabalho foi realizado com o objectivo de esclarecer qual o significado funcional da adenosina na quimiorrecepo no CB em animais controlo e em animais submetidos a hipoxia crnica mantida. Para alcanar este objectivo investigou-se: 1) o efeito da hipxia moderada sobre a libertao de adenosina numa preparao in vitro de CB e a especificidade desta mesma libertao comparativamente com outros tecidos no quimiossensitivos, assim como as vias metablicas de produo e libertao de adenosina no CB em normoxia e hipxia; 2) a modulao da libertao de adenosina/ATP das clulas quimiorreceptoras do CB por receptores nicotnicos de ACh; 3) os efeitos da cafena no controlo perifrico da ventilao e a identidade dos receptores de adenosina envolvidos nos efeitos da adenosina e da cafena nos quimiorreceptores do CB; 4) as interaces entre os receptores D2 de dopamina e os receptores A2B de adenosina que modulam a libertao de catecolaminas (CA) no CB de rato e; 5) o efeito da ingesto crnica de cafena, isto , o contnuo bloqueio e dos receptores de adenosina, simulando assim o consumo crnico da cafena, tal como ocorre na populao humana mundial e principalmente no ocidente, na funo do corpo carotdeo em ratos controlo e em ratos submetidos a hipoxia crnica. Os mtodos utilizados neste trabalho incluram: tcnicas de biologia molecular como imunocitoqumica e western-blot; tcnicas bioqumicas, tais como a quantificao de neurotransmissores por HPLC, bioluminescncia e mtodos radioisotpicos; tcnicas electrofisiolgicas como o registro de potenciais elctricos do nervo do seio carotdeo in vitro; e registros ventilatrios in vivo em animais no anestesiados e em livre movimento (pletismografia). Observou-se que: 1) a especificidade dos quimiorreceptores do CB como sensores de O2 est correlacionada com o baixo limiar de libertao de adenosina em resposta hipxia dado que a libertao de adenosina do CB aumenta 44% em resposta a uma hipxia moderada (10% O2), que no entanto no um estmulo suficientemente intenso para evocar a libertao de adenosina do gnglio cervical superior ou do tecido arterial. Observou-se tambm que aproximadamente 40% da adenosina libertada pelo CB provm do catabolismo extracelular do ATP quer em normxia quer em hipxia moderada, sendo que PO2 reduzidas induzem a libertao de adenosina via activao do sistema de transporte equilibrativo ENT1. 2) a ACh modula a libertao de adenosina /ATP do CB em resposta hipoxia moderada sugerindo que o papel excitatrio da ACh na actividade quimiossensora inclui a activao indirecta de receptores purinrgicos pela adenosina e ATP, indicando que a adenosina e o ATP poderiam actuar como mediadores importantes no processo de quimiotransduco uma vez que: a) a activao dos receptores nicotnicos de ACh no CB em normxia estimula a libertao de adenosina (max 36%) provindo aparentemente da degradao extracelular do ATP. b) a caracterizao farmacolgica dos receptores nicotnicos de ACh envolvidos na estimulao da libertao de adenosina do CB revelou que os receptores nicotnicos de ACh envolvidos so constitudos por subunidades 42. 3) a adenosina modula a libertao de catecolaminas das clulas quimiorreceptoras do CB atravs de receptores de adenosina A2B dado que: a)a cafena, um antagonista no selectivo dos receptores de adenosina, inibiu a libertao de CA quer em normxia quer em resposta a estmulos de baixa intensidade sendo ineficaz na libertao induzida por estmulos de intensidade superior; b) o DPCPX e do MRS1754 mimetizaram os efeitos da cafena no CB sendo o SCH58621 incapaz de induzir a libertao de CA indicando que os efeitos da cafena seriam mediados por receptores A2B de adenosina cuja presena nas clulas quimiorreceptoras do CB demonstramos por imunocitoqumica. 4) a aplicao aguda de cafena inibiu em 52% a actividade quimiossensora do CSN induzida pela hipxia sendo este efeito mediado respectivamente por receptores de adenosina A2A ps-sinpticos e A2B pr-sinpticos indicando que a actividade quimiossensora induzida pela hipxia controlada pela adenosina. 5) existe uma interaco entre os receptores A2B e D2 que controla a libertao de CA do corpo carotdeo de rato uma vez que: a) os antagonistas dos receptores D2, domperidona e haloperidol, aumentaram a libertao basal e evocada de CA das clulas quimiorreceptoras confirmando a presena de autorreceptores D2 no CB de rato que controlam a libertao de CA atravs de um mecanismo de feed-back negativo. b) o sulpiride, um antagonista dos receptores D2, aumentou a libertao de CA das clulas quimiorreceptoras revertendo o efeito inibitrio da cafena sobre esta mesma libertao; c) a propilnorapomorfina, um agonista D2 inibiu a libertao basal e evocada de CA sendo este efeito revertido pela NECA, um agonista dos receptores A2B. O facto de a NECA potenciar o efeito do haloperidol na libertao de CA sugere que a interaco entre os receptores D2 e A2B poderia tambm ocorrer ao nvel de segundos mensageiros, como o cAMP. 6) a ingesto crnica de cafena em ratos controlo (normxicos) no alterou significativamente a funo basal do CB medida como a dinmica dos seus neurotransmissores, dopamina, ATP e adenosina e como actividade quimiossensora do CSN. Contrariamente aos efeitos basais, a ingesto crnica de cafena facilitou a resposta hipxia, dado que aumentou o efeito no volume minuto respiratrioapresentando-se tambm uma clara tendncia para aumentar a actividade quimiossensora do CSN e aumentar a libertao de ATP e dopamina.7) aps um perodo de 15 dias de hipxia crnica era evidente o fenmeno de aclimatizao dado que as respostas ventilatrias hipxia se encontram aumentadas, assim como a actividade quimiossensora do CSN basal e induzida pela hipxia. As alteraes observadas no metabolismo da dopamina, assim como na libertao basal de dopamina e de adenosina poderiam contribuir para a aclimatizao durante a hipoxia crnica. A libertao aumentada de adenosina em resposta hipxia aguda em ratos hipxicos crnicos sugere um papel da adenosina na manuteno/aumento das respostas ventilatrias hipxia aguda durante a hipxia crnica. Observou-se tambm que a libertao de ATP induzida pela hipxia aguda se encontra diminuda em hipxia crnica, contudo a ingesto crnica de cafena reverteu este efeito para valores similares aos valores controlo, sugerindo que a adenosina possa modular a libertao de ATP em hipxia crnica. 8) a ingesto crnica de cafena em ratos hipxicos crnicos induziu o aumento do metabolismo de CA no CB, medido como expresso de tirosina hidroxilase, contedo, sntese e libertao de CA. 9) a ingesto crnica de cafena no provocou quaisquer alteraes na actividade quimiossensora do CSN em ratos hipxicos crnicos no entanto, as respostas do CSN hipxia aguda intensa e moderada e hipercapnia encontram-se diminudas. Este efeito inibitrio que provm da ingesto crnica de cafena parece ser compensado ao nvel dos quimiorreceptores centrais dado que os parmetros ventilatrios em condies basais e em resposta hipoxia aguda no se encontram modificados em ratos expostos durante 15 dias a uma atmosfera hipxica. Resumindo podemos assim concluir que a adenosina quer em situaes de hipoxia aguda quer em condies de hipoxia crnica tem um papel excitatrio na actividade quimiossensora do CB actuando directamente nos receptores A2A presentes ps-sinapticamente no CSN, assim como facilitando a libertao de dopamina pr-sinapticamente via receptores A2B presentes nas clulas quimiorreceptoras. A interaco negativa entre os receptores A2B e D2 observadas nas clulas quimiorreceptoras do CB poderia explicar o aumento do metabolismo de CA observado aps a ingesto crnica de cafena em animais hipxicos. Conclui-se ainda que durante a aclimatizao hipxia a aco inibitria da cafena, em termos de resposta ventilatria, mediada pelos quimiorreceptores perifricos compensada pelos efeitos excitatrios desta xantina ao nvel do quimiorreceptores centrais.------- RESUMEN Los cuerpos carotdeos (CB) son rganos emparejados que estn localizados en la bifurcacin de la arteria cartida comn. Estos rganos son sensibles a variaciones en la PaO2, en la PaCO2, pH y temperatura siendo responsables de la hiperventilacin que ocurre en respuesta a la hipoxia, contribuyendo tambin a la hiperventilacin que acompaa a la acidosis metablica y respiratoria. Las clulas quimiorreceptoras (tipo I o glmicas) del cuerpo carotdeo responden a las variaciones de gases arteriales liberando neurotransmissores que activan las terminaciones sensitivas del nervio del seno carotdeo (CSN) llevando la informacin al centro respiratorio central. Todava esta por clarificar cual el neurotransmisor (o neurotransmisores) responsable por la sealizacin hipxica en el CB. La adenosina es un neurotransmisor excitatrio en el CB ya que aumenta la actividad del CSN e induce la hiperventilacin a travs de la activacin de receptores de adenosina del subtipo A2. La importancia de estos efectos de la adenosina en la quimiorrecepcin, descritos en ratas y gatos, ha sido fuertemente reforzada por resultados obtenidos en voluntarios sanos en los que la infusin intravenosa de adenosina induce hiperventilacin y dispnea, efectos ests que han sido atribuidos a una activacin del CB ya que la adenosina no cruza la barrera hemato-encefalica y el efecto es tanto ms grande cuanto ms cercana del CB es la administracin. Este trabajo ha sido realizado con el objetivo de investigar cual el significado funcional de la adenosina en la quimiorrecepcin en el CB en animales controlo y en animales sometidos a hipoxia crnica sostenida. Para alcanzar este objetivo se ha estudiado: 1) el efecto de la hipoxia moderada en la liberacin de adenosina en una preparacin in vitro de CB y la especificidad de esta liberacin en comparacin con otros tejidos no-quimiosensitivos, as como las vas metablicas de produccin y liberacin de adenosina del rgano en normoxia y hipoxia; 2) la modulacin de la liberacin de adenosina/ATP de las clulas quimiorreceptoras del CB por receptores nicotnicos de ACh; 3) los efectos de la cafena en el controlo perifrico de la ventilacin y la identidad de los receptores de adenosina involucrados en los efectos de la adenosina y cafena en los quimiorreceptores del CB; 4) las interacciones entre los receptores D2 de dopamina y los receptores A2B de adenosina que modulan la liberacin de catecolaminas (CA) en el CB de rata y; 5) el efecto de la ingestin crnica de cafena, es decir, el bloqueo sostenido de los receptores de adenosina, simulando la dependencia de cafena observada en la populacin mundial del occidente, en la funcin del CB en ratas controlo y sometidas a hipoxia crnica sostenida. Los mtodos utilizados en este trabajo incluirn: tcnicas de biologa molecular como imunocitoqumica y western-blot; tcnicas bioqumicas, tales como la cuantificacin de neurotransmissores por HPLC, bioluminescencia y mtodos radioisotpicos; tcnicas electrofisiolgicas como el registro de potenciales elctricos del nervio do seno carotdeo in vitro; y registros ventilatrios in vivo en animales no anestesiados y en libre movimiento (pletismografia). Se observ que: 1) la sensibilidad de los quimiorreceptores de CB esta correlacionada con un bajo umbral de liberacin de adenosina en respuesta a la hipoxia ya que en respuesta a una hipoxia moderada (10% O2) la liberacin de adenosina en el CB aumenta un 44%, sin embargo esta PaO2 no es un estimulo suficientemente fuerte para inducir la liberacin de adenosina del ganglio cervical superior o del tejido arterial; se observ tambin que aproximadamente 40% de la adenosina liberada del CB proviene del catabolismo extracelular del ATP en normoxia y en hipoxia moderada, y que bajas PO2 inducen la liberacin de adenosina va activacin del sistema de transporte equilibrativo ENT1. 2) la ACh modula la liberacin de adenosina /ATP del CB en respuesta a la hipxia moderada lo que sugiere que el papel excitatrio de la ACh en la actividad quimiosensora incluye la activacin indirecta de receptores purinrgicos por la adenosina y el ATP, indicando que la adenosina y el ATP pueden actuar como mediadores importantes en el proceso de quimiotransduccin ya que: a) la activacin de los receptores nicotnicos de ACh en el CB en normoxia estimula la liberacin de adenosina (max 36%) que aparentemente proviene de la degradacin extracelular del ATP. Se observ tambin que este aumento de adenosina en el CB en hipoxia ha sido antagonizado parcialmente por antagonistas de estos mismos receptores; b) la caracterizacin farmacolgica de los receptores nicotnicos de ACh involucrados en la estimulacin de la liberacin de adenosina del CB ha revelado que los receptores nicotnicos de ACh involucrados son constituidos por sub-unidades 42. 3) la adenosina modula la liberacin de CA de las clulas quimiorreceptoras del CB a travs de receptores de adenosina A2B ya que: a) la cafena, un antagonista no selectivo de los receptores de adenosina, ha inhibido la liberacin de CA en normoxia y en respuesta a estmulos de baja intensidad siendo ineficaz en la liberacin inducida por estmulos de intensidad superior; b) el DPCPX y el MRS1754 ha mimetizado los efectos de la cafena en el CB y el SCH58621 ha sido incapaz de inducir la liberacin de CA lo que sugiere que los efectos de la cafena son mediados por receptores A2B de adenosina que estn localizados pr-sinapticamente en las clulas quimiorreceptoras del CB. 4) la aplicacin aguda de cafena ha inhibido en 52% la actividad quimiosensora del CSN inducida por la hipoxia siendo este efecto mediado respectivamente por receptores de adenosina A2A ps-sinpticos y A2B pr-sinpticos lo que indica que la actividad quimiosensora inducida por la hipoxia es controlada por la adenosina. 5) existe una interaccin entre los receptores A2B y D2 que controla la liberacin de CA del CB de rata ya que: a) el sulpiride, un antagonista de los receptores D2, ha aumentado la liberacin de CA de las clulas quimiorreceptoras revertiendo el efecto inhibitorio de la cafena sobre esta misma liberacin; b) los antagonistas de los receptores D2, domperidona y haloperidol, han aumentado la liberacin basal e evocada de CA de las clulas quimiorreceptoras confirmando la presencia de autorreceptores D2 en el CB de rata que controlan la liberacin de CA a travs de un mecanismo de feed-back negativo; c) la propilnorapomorfina, un agonista D2, ha inhibido la liberacin basal e evocada de CA sendo este efecto revertido por la NECA, un agonista de los receptores A2B. Ya que la NECA potencia el efecto del haloperidol en la liberacin de CA la interaccin entre los D2 y A2B puede tambin ocurrir al nivel de segundos mensajeros, como el cAMP. 6) la ingestin crnica de cafena en ratas controlo (normxicas) no ha cambiado significativamente la funcin basal del CB medida como la dinmica de sus neurotransmisores, dopamina, ATP y adenosina y como actividad quimiosensora del CSN. Al revs de lo que pasa con los efectos bsales, la ingestin crnica de cafena facilit la respuesta a la hipxia, ya que ha aumentado la respuesta ventilatria medida como volumen minuto presentando tambin una clara tendencia para aumentar la actividad quimiosensora del CSN y aumentar la liberacin de ATP y dopamina. 7. Despus de un perodo de 15 das de hipoxia crnica se puede observar el fenmeno de climatizacin ya que las respuestas ventilatrias a la hipoxia estn aumentadas, as como la actividad quimiosensora del CSN basal e inducida por la hipoxia. Los cambios observados en el metabolismo de la dopamina, as como en la liberacin basal de dopamina y de adenosina podran contribuir para la climatizacin en hipoxia crnica. El aumento en la liberacin de adenosina en respuesta a la hipoxia aguda en ratas sometidas a hipoxia crnica sugiere un papel para la adenosina en el mantenimiento/aumento de las respuestas ventilatrias a la hipoxia aguda en hipoxia crnica sostenida. Se ha observado tambin que la liberacin de ATP inducida por la hipoxia aguda est disminuida en hipoxia crnica y que la ingestin crnica de cafena reverte este efecto para valores similares a los valores controlo, sugiriendo que la adenosina podra modular la liberacin de ATP en hipoxia crnica. 8. la ingestin crnica de cafena ha inducido el aumento del metabolismo de CA en el CB en ratas hipxicas crnicas, medido como expresin de la tirosina hidroxilase, contenido, sntesis y liberacin de CA. 9. la ingestin crnica de cafena no ha inducido cambios en la actividad quimiosensora del CSN en ratas hipxicas crnicas sin embargo las respuestas do CSN a una hipoxia intensa y moderada y a la hipercapnia estn disminuidas. Este efecto inhibitorio que es debido a la ingestin crnica de cafena es compensado al nivel de los quimiorreceptores centrales ya que los parmetros ventilatrios en condiciones bsales y en respuesta a la hipoxia aguda no estn modificados en ratas expuestas durante 15 das a una atmsfera hipxica. Resumiendo se puede concluir que la adenosina en situaciones de hipoxia aguda as como en hipoxia crnica tiene un papel excitatrio en la actividad quimiosensora del CB actuando directamente en los receptores A2A localizados ps-sinapticamente en el CSN, as como controlando la liberacin de dopamina pr-sinaptica va receptores A2B localizados en las clulas quimiorreceptoras. Las interacciones entre los receptores A2B y D2 observadas en las clulas quimiorreceptoras del CB podran explicar el aumento del metabolismo de CA observado despus de la ingestin crnica de cafena en animales hipxicos. Por fin, pero no menos importante se puede concluir que durante la climatizacin a la hipoxia la accin inhibitoria de la cafena, medida como respuesta ventilatria, mediada por los quimiorreceptores perifricos es compensada por los efectos excitatrios de esta xantina al nivel de los quimiorreceptores centrales.
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The study is a randomized trial using recombinant DNA vaccine to determine whether an intramuscular 10 g dose or intradermal 2 g induces satisfactory anti-HBs levels compared to the standard dose of intramuscular 20 g. participants were 359 healthy medical and nurse students randomly allocated to one of the three groups: Group I - IM 20 g; Group II - IM 10 g; Group III - ID 2 g at 0, 1 and 6 months. Anti-HBs titres were measured after complete vaccine schedule by ELISA/Pasteur. Baseline variables were similar among groups and side effects were mild after any dose. Vaccinees in the IM-10 g group had seroconversion rate and geometric mean titre (GMT 2344 IU L-1), not significant different from the IM-20 g group (GMT 4570 IU L-1). On the contrary, 21.4% of the ID - 2 g recipients mount antibody concentration below 10 IU L1 and GMT of 91 IU L-1, a statiscally significant difference compared with the standard schedule IM-20 g (p < 0.001). A three dose regimen of half dosse IM could be considered an appropriate schedule to prevent hepatitis B in young health adults which is of relevance to the expansion of hepatitis B vaccine programme
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The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.
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Dissertation presented to obtain a PhD degree in Biology/ Molecular Biology by the Universidade Nova de Lisboa, Instituto de Tecnologia Qumica e Biolgica
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RESUMO: A partir da desinstitucionalizao psiquitrica, a nfase nas polticas pblicas de sade mental passou para os servios comunitrios e para perodos mais curtos de hospitalizao. As famlias, ento, tornaram-se as principais provedoras de cuidados cotidianos e de apoio aos pacientes. As dificuldades e o despreparo em assumir este novo papel tm gerado um sentimento de sobrecarga nos familiares, o que pode afetar sua sade fsica e mental. Vrios estudos investigaram as consequncias de se tornar um cuidador de um paciente psiquitrico, mas poucos pesquisaram o impacto na sade mental desses cuidadores. A presente pesquisa investigou a relao entre a sobrecarga e a sade mental dos familiares cuidadores de pacientes psiquitricos. Participaram deste estudo 74 familiares cuidadores de pacientes com diagnstico de esquizofrenia, atendidos no ambulatrio do Servio de Referncia em Sade Mental, da cidade de Divinpolis, MG. Os familiares participaram de uma entrevista estruturada. Nela foram aplicadas a Escala de Avaliao da Sobrecarga dos Familiares de Pacientes Psiquitricos (FBIS-BR) e, para avaliar a sade mental dos cuidadores, a Escala de Depresso de Beck (BDI). Foram realizadas anlises estatsticas descritivas, univariadas e multivariadas. Os resultados mostraram que a maioria dos cuidadores era do sexo feminino (78,40%), pais (62,20%) e com idade mdia de 59,14 anos. Os cuidadores apresentaram uma mdia de sobrecarga global objetiva de 2,05 (DP 0,54), em uma escala de 1 a 5 pontos, e uma mdia de sobrecarga global subjetiva de 2,44 (DP 0,71), em uma escala de 1 a 4 pontos. Os resultados da escala BDI mostraram que 42 cuidadores poderiam ser classificados com depresso mnima (56,80%), 17 com depresso leve (23,00%), 7 com depresso moderada (9,50%) e 8 com depresso grave (10,80%). Foram encontradas correlaes positivas significativas entre o grau de sobrecarga global e das subescalas e o nvel de depresso. As anlises multivariadas mostraram que o principal preditor de depresso dos cuidadores foi a sobrecarga global subjetiva. Outros preditores foram a obrecarga objetiva das rotinas dirias e da superviso dos comportamentos problemticos dos pacientes e a sobrecarga subjetiva das preocupaes com o paciente. As informaes levantadas mostraram o impacto do papel de cuidador na sade mental dos familiares e apontaram para a necessidade de uma maior ateno, por parte dos gestores e profissionais da rea, aos cuidadores de pacientes psiquitricos.----------ABSTRACT: The emphasis in public policy on mental health was transferred to community services and for shorter periods of hospitalization from the psychiatric deinstitutionalization. Then the families become the first provider of daily care and support to patients. The difficulties and unprepared to assume this new role has generated a sense of overload in the relatives, which can affect your physical and mental health. Several studies have investigated the consequences of becoming a caregiver of a psychiatric patient, but few scholars have researched the impact on the mental health of caregivers. The present study has investigated the relationship between overload and mental health of family caregivers of psychiatric patients. The study included 74 family caregivers of patients with schizophrenia and outpatient clinic of the Department of Mental Health Reference, in Divinpolis, Minas Gerais, Brazil. The Rating Scale Burden of Relatives of Psychiatric Patients and the scale of Beck Depression Inventory (BDI) to assess the mental health of caregivers were applied in the interview. Descriptive statistics and univariate and multivariate analysis have performed. The results showed that the majority of caregivers were female (78.40%), parents (62.20%) and mean age of 59.14 years. The caregivers had an average burden overall objective of 2.05 ( 0.54) on a scale of 1 to 5 points, and a subjective global average burden of 2.44 ( 0.71) in a scale of 1 to 4 points. The results of the BDI showed that 42 caregivers could be classified with minimal depression (56.80%), 17 with mild depression (23.00%), 7 with moderate depression (9.50%) and 8 with severe depression (10 80%). Significant positive correlations were found between the degree of overloading and global subscales and depression levels. Multivariate analysis showed that the main predictor of caregivers' depression was the global subjective burden. Other predictors were the objective burden of daily routines and supervision of problem behaviors of patients and subjective burden of the concerns about patient. The resulting information showed the impact of caregiver role in the mental health of relatives and pointed to the need for higher attention of managers and professionals to caregivers of psychiatric patients.
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From January, 1984 to December, 1996, 422 patients (ages 9 m-99 y, median 29 y) were admitted after being bitten by spiders which were brought and identified as Phoneutria spp. Most of the bites occurred at March and April months (29.2%), in the houses (54.5%), during the day (76.5%), and in the limbs (feet 40.9%, hands 34.3%). Upon hospital admission, most patients presented only local complaints, mainly pain (92.1%) and edema (33.1%) and were classified as presenting mild (89.8%), moderate (8.5%) and severe (0.5%) envenomation. Few patients (1.2%) did not present signs of envenomation. Severe accidents were only confirmed in two children (9 m, 3 y). Both developed acute pulmonary edema, and the older died 9 h after the accident. Patients more than 70 year-old had a significantly greater (p<0.05) frequency of moderate envenomations compared to the 10-70-year-old individuals. Proceedings to relief local pain were frequently performed (local anesthesia alone 32.0%, local anesthesia plus analgesics 20.6% and oral analgesics alone 25.1%). Only 2.3% of the patients (two cases classified as severe and eight as moderate, eight of them in children) were treated with i.v. antiarachnid antivenom. No antivenom early reaction was observed. In conclusion, accidents involving the genus Phoneutria are common in the region of Campinas, with the highest risk groups being children under 10 years of age and adults over 70 years of age. Cases of serious envenomation are rare (0.5%).
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Hantavirus pulmonary syndrome (HPS) has been recognized recently in Brazil, where 28 cases have been reported as of September 1999. We report here the clinical and laboratory findings of three cases whose diagnoses were confirmed serologically. All the patients were adults who presented a febrile illness with respiratory symptoms that progressed to respiratory failure that required artificial ventilation in two of them. Laboratory findings were most of the time consistent with those reported in the United States in patients infected with the Sin Nombre virus, and included elevated hematocrit and thrombocytopenia; presence of atypical lymphocytes was observed in one patient. The chest radiological findings observed in all the patients were bilateral, diffuse, reticulonodular infiltrates. Two patients died. Histopathological examination of the lungs of these patients revealed interstitial and alveolar edema, alveolar hemorrhage, and mild interstitial pneumonia characterized by infiltrate of immunoblasts and mononuclear cells. In the epidemiologic investigation of one of the cases, serologic (ELISA) tests were positive in 3 (25%) out of 12 individuals who shared the same environmental exposure. HPS should be included in the differential diagnosis of interstitial pneumonia progressing to acute respiratory failure.
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RESUMO - A Paralisia Cerebral (PC) deve ser olhada como uma patologia do neurodesenvolvimento: a infncia um perodo de actividade exploratria por essncia, a restrio motora condiciona as vrias reas do desenvolvimento. Contextos, apoios, oportunidades e experincias de vida sero determinantes no desenvolvimento de todo o seu potencial. Objectivos/finalidade: Identificar, descrever, comparar e analisar factores de risco associados PC, sua caracterizao multidimensional e integrao escolar aos 5 e 10 anos. Procurouse contribuir para a sua preveno primria e secundria, e obter dados para planeamento e implementao dos programas de apoio. Mtodos: Adoptouse a abordagem do Programa Nacional de Vigilncia da Paralisia Cerebral (PNVPC) e da Surveillance of Cerebral Palsy in Europe (SCPE). Analisaramse factores de risco, competncias funcionais, dfices associados, severidade e integrao escolar de duas populaes de Lisboa e Vale do Tejo, (nascimento 1996/19972001/2002 e prevalncia aos 5 e 10 anos). Descreveramse os dados, efectuaramse correlaes, aplicaramse testes de independncia e compararamse com dados dos nadovivos, dados nacionais e europeus. Analisaramse os factores que influenciaram a integrao escolar atravs de mtodos de regresso logstica. Resultados/Concluses/Recomendaes: 1,65 e 1,57 dos nadovivos desenvolveram PC; a prevalncia aos 5 anos foi de 1,7 e de 1,48; 5,9% e 7,9% faleceram antes dos 5 anos. Em 2001/2002 verificouse aumento de: PC espstica bilateral2/3membros, prematuridade, causa posneonatal, nveis funcionais ligeiros e graves; percentil estaturoponderal <3 (5anos). Diminuio de: disquinsia, anxia e alguns dfices associados. Destacaramse as associao: prematuridade e PC espstica bilateral 2/3membros; nascer de termo e anxia, disquinsia, primparas, dfices associados e severidade; infeco prnatal e QI<50, epilepsia e severidade; causa posneonatal e PC espstica bilateral4membros e mltiplos dfices. Aos 5 anos, as variveis explicativas para a no incluso escolar foram: QI<50 e epilepsia; uma elevada percentagem de crianas com PC moderada/grave encontravase integrada; 75% das que se encontravam desintegradas mantiveramse nesta situao aos 10. Nesta idade, as variveis explicativas para a no incluso escolar foram: QI<50 e motricidade fina; 35,1% encontravase fora do ensino regular; 4,5%, embora em idade de escolaridade obrigatria, no frequentavam qualquer estabelecimento escolar. Informao sistematizada, abrangente, objectiva, simples e acessvel, sobre novos casos de PC, factores de risco, prevalncia em idadeschave e caracterizao multidimensional constitui uma ferramenta clnica e epidemiolgica, que deve sustentar as polticas de sade, educacionais e sociais, contribuindo para a permanncia destas crianas no ensino regular, trazendo s crianas e famlias o suporte que as encorajem e sustentem nestes processos. ABSTRACT ------- Cerebral Palsy (CP) must be recognized as a neurodevelopmental disorder: childhood is, on its nature, a period for exploring the environment and therefore motor deficit interferes with all developmental areas. The context, support, opportunities and life experiences are determinants for the development of his full potential. Objective/Aim: To identify, describe, compare and analyze CP risk factors the multidimensional characterization and school integration levels at the age of 5 and 10 years. We aim to contribute to CP primary and secondary prevention and provide information for service planning and implementation of support programs. Methods: The approach of National Cerebral Palsy Surveillance Programme (NCPSP) and Surveillance of Cerebral Palsy in Europe (SCPE) were used. For two groups of children from Lisboa e Vale do Tejo region, birth data 1996/19972001/2002 and prevalence at 5 and 10 years, were analyzed: CP risk factors, functional ability, associated impairments, severity and school integration settings. Data collected was described, analyzed using correlations, applied tests of independence and compared with new born data, national data and european data. To analyze the factors related to school inclusive settings, logistic regression was appealed. Results/Conclusions/Recommendations: 1,65% and 1,57 of the newborn alive developed CP. The prevalence at 5 years was 1,7 and 1,48 5,9% and 7,9% died before their 5th birthday. Bilateral spastic CP 2/3limb, preterm birth, cases of postneonatal origin, mild and sever functional impairment; weight and height percentile <3 at 5 years old Increased in 2001. Decreased dyskinetic CP, anoxia and some additional imparments. Were identified among other the association between prematurity and spastic bilateral CP2/3 members; born at term and anoxia, dyskinetic CP, first child, associated impairments and severity; prenatal infection and IQ<50, epilepsy and severity; postneonatal cause and spastic bilateral CP4 members and associated impairments. At 5yearsold the more explanatory variables for not be in a school inclusive settings were IQ<50 and epilepsy, a high percentage of children with moderate/severe CP was attending regular school, but most children who were out of inclusive settings at 5 years continue on this situations at 10yearsold. At this age the more explanatory variables for not be in a school inclusive settings were: IQ<50 and upper limb function; 35,1% were out of regular school; 4,5%, even in compulsory school age, are out of school. Standardized comprehensive, objective, simple and accessible information about CP new cases, risk factors, prevalence in the keyage and children multidimensional characterization constitutes a clinical and epidemiological tool that should sustain health, educational and social policy. This would support the continuity of these children in regular schools, encouraging g them and their families in these processes.
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Between 1992 and 1997, 790 blood donors with anti-HCV EIA-2 strongly reagent (relationship between the sample optical density/cut-off > 3) detected at the blood bank serological screening, were evaluated in ambulatory environment. They were all negative for Chagas disease, syphilis, hepatitis B (HBsAg) and AIDS. Blood samples were collected at the first ambulatorial evaluation, for hemogram, biochemical tests and new serological tests for HCV (anti-HCV EIA-2). In blood samples of 226 repeatedly reagent anti-HCV EIA-2 blood donors, supplementary "immunoblot" test for HCV (RIBA-2) was used. In 209 donors, the presence of HCV-RNA was investigated by the PCR test. The abdominal ultrasonography was realized in 366 donors. In 269 patients liver biopsy was performed for the histopathological study. The follow-up of blood donors showed that 95.6% were repeatedly EIA-2 reagent, 94% were symptomless and denied any hepatitis history, with only 2% mentioning previous jaundice. In 47% of this population at least one risk factor has been detected for the HCV transmission, the use of intravenous drugs being the main one (27.8%). Blood transfusion was the second factor for HCV transmission (27.2%). Hepatomegaly was detected in 54% of the cases. Splenomegaly and signs of portal hypertension have seldom been found in the physical examination, indicating a low degree of hepatic compromising in HCV. Abdominal ultrasound showed alterations in 65% of the subjects, being the steatosis the most frequent (50%). In 83.5% of the donors submitted to the liver biopsy, the histopathological exam showed the presence of chronic hepatitis, usually classified as active (89%) with mild or moderate grade in most of the cases (99.5%). The histopathological exam of the liver was normal in 1.5% of blood donors. The RIBA-2 test and the HCV-RNA investigation by PCR were positive in respectively 91.6 and 75% of the anti-HCV EIA-2 reagent donors. The HCV-RNA research was positive in 82% of the RIBA-2 positive subjects, in 37.5% of the indeterminate RIBA-2 donors and in 9% of the negative RIBA-2 donors. Chronic hepatitis has also been observed in 50% of the histopathological exams of the anti-HCV EIA-2 reagent donors which were indeterminate RIBA-2. Among 18 blood donors with minimal changes histopathological exam 11 (61%) were HCV-RNA positive. Our blood donors anti-HCV reagent generally had clinical, laboratorial and histopathological features observed in patients with chronic HCV hepatitis and a high proportion could be identified in interviews and medical evaluation realized in blood blanks. Generally, these HCV infected donors are identified and discharged only by the serological tests results.
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Response to treatment with antimonial drugs varies considerably depending on the parasite strain involved, immune status of the patient and clinical form of the disease. Therapeutic regimens with this first line drug have been frequently modified both, in dose and duration of therapy. A regimen of 20 mg/kg/day of pentavalent antimony (Sb5+) during four weeks without an upper limit on the daily dose is currently recommended for mucosal disease ("espundia"). Side-effects with this dose are more marked in elderly patients, more commonly affected by this form of leishmaniasis. According to our experience, leishmaniasis in Rio de Janeiro responds well to antimony and, in cutaneous disease, high cure rates are obtained with 5 mg/kg/day of Sb5+ during 30 to 45-days. In this study a high rate of cure (91.4%) employing this dose was achieved in 36 patients with mild disease in this same geographic region. Side-effects were reduced and no antimony refractoriness was noted with subsequent use of larger dose in patients that failed to respond to initial schedule.
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Dissertation presented to obtain the Ph.D degree in Biochemistry, Plant Physiology
Aseptic meningitis in a large MMR vaccine campaign (590,609 people) in Curitiba, Paran, Brazil, 1998
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The aseptic meningitis after Measles-Mumps-Rubella vaccine (MMR) is a well recognized complication, and different incidences have been observed in several studies. We retrospectively analyzed forty cases of aseptic meningitis, during a large public immunization campaign (1998) in Curitiba, Southern Brazil (590,609 people), admitted in our Service. The vaccine utilized was Leningrad-3-Zagreb mumps strain, Edmonston-Zagreb measles strain, and RA 27#3 rubella strain. In all county, a total number of 87 cases were reported, resulting in a incidence of 1.7 cases per 10,000 given doses . The mean age was 23.7 12.8 years. The female:male ratio was 1.35:1. Severe headache with meningismus (92.5%), fever (87.5%), nausea/vomiting (82.5%) were the most common clinical findings. Three cases (7.5%) developed mild mumps. All patients underwent cerebrospinal fluid (CSF) tap with the following findings: mononuclear pleocytosis from 100 to 500 cells/mm in 17 cases (42.5%; 257.5 260.6 cells/mm); increased protein 28 cases (67.5%; 92.1 76.9 mg/dL); glucose was normal in all cases (56.8 11.2 mg/dL) except in 4 (10%) cases, which presented less than 44 mg/dL. All serological tests (latex to bacterial meningitis, Cryptococcus, cysticercosis, VDRL) and bacteriological cultures were negative. Virus identification were also negative in 8 samples. None of the patients had neurological deficits or related symptoms after one year of onset. We believe the benefit of vaccination clearly outweights the incidence of benign vaccine-associated meningitis.
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From January, 1984 to March, 1999, 73 children under 15 y old (ages 1-14 y, median 9 y) were admitted after being bitten by snakes of the genus Bothrops. Twenty-six percent of the children were classified as mild envenoming, 50.7% as moderate envenoming and 20.6% as severe envenoming. Two patients (2.7%) showed no signs of envenoming. Most of the patients presented local manifestations, mainly edema (94.5%), pain (94.5%) ecchymosis (73.9%) and blisters (11%). Local and/or systemic bleeding was observed in 28.8% of the patients. Before antivenom (AV) administration, blood coagulation disorders were observed in 60.7% (incoagulable blood in 39.3%) of the 56 children that received AV only in our hospital. AV early reactions, most of which were considered mild, were observed in 44.6% of these cases (in 15/30 patients not pretreated and in 10/26 patients pretreated with hydrocortisone and histamine H1 and H2 antagonists). The main clinical complications observed were local infection (15.1%), compartment syndrome (4.1%), gangrene (1.4%) and acute renal failure (1.4%). No deaths were recorded. There were no significant differences with regard to severity of envenoming versus the frequency of blood coagulation disorders among the three categories of envenoming (p = 0.75) or in the frequency of patients with AV early reactions between the groups that were and were not pretreated (p = 0.55). The frequency of local infection was significantly greater in severe cases (p < 0.001). Patients admitted more than 6 h after the bite had a higher risk of developing severe envenoming (p = 0.04).
