The Effect of Urocortin 1 on Motility in Isolated, Vascularly Perfused Rat Colon / 대한소화기학회지

BACKGROUND/AIMS: Urocortin 1, a corticotropin-releasing factor related peptide, increases colonic motility under stressful conditions. We investigated the effect of urocortin 1 on colonic motility using an experimental model with isolated rat colon in which the blood flow and intestinal nerves were preserved. Furthermore, we assessed whether this effect was mediated by adrenergic or cholinergic nerves. METHODS: Colonic motility was measured in the proximal and distal parts of resected rat colon. The colon resected from the peritoneum was stabilized, and then urocortin 1 (13.8, 138, 277, and 1,388 pM) was administered via a blood vessel. Motility index was measured in the last 5 min of the 15 min administration of urocortin 1 and expressed as percentage change from baseline. Subsequently, the change in motility was measured by perfusing urocortin 1 in colons pretreated with phentolamine, propranolol, hexamethonium, atropine, or tetrodotoxin. RESULTS: At concentrations of 13.8, 138, 277, and 1,388 pM, urocortin 1 increased the motility of proximal colon (20.4+/-7.2%, 48.4+/-20.9%, 67.0+/-25.8%, and 64.2+/-20.9%, respectively) and the motility of distal colon (3.3+/-3.3%, 7.8+/-7.8%, 71.1+/-28.6%, and 87.4+/-32.5%, respectively). The motility induced by urocortin 1 was significantly decreased by atropine to 2.4+/-2.4% in proximal colon and 3.4+/-3.4% in distal colon (p<0.05). However, tetrodotoxin, propranolol, phentolamine, and hexamethonium did not inhibit motility. CONCLUSIONS: Urocortin 1 increased colonic motility and it is considered that this effect was directly mediated by local muscarinic cholinergic receptors.

Pattern of Maxillofacial Fractures in Severe Multiple Trauma Patients: A 7-year Prospective Study

The incidence of facial trauma is high. This study has the primary objective of documenting and cataloging maxillofacial fractures in polytrauma patients. From a total of 1229 multiple trauma cases treated at the Emergency Room of the Santo Antonio Hospital - Oporto Hospital Center, Portugal, between August 2001 and December 2007, 251 patients had facial wounds and 209 had maxillofacial fractures. Aged ranged form 13 to 86 years. The applied selective method was based on the presence of facial wound with Abbreviated Injury Scale ≥1. Men had a higher incidence of maxillofacial fractures among multiple trauma patients (86.6%) and road traffic accidents were the primary cause of injuries (69.38%). Nasoorbitoethmoid complex was the most affected region (67.46%) followed by the maxilla (57.42%). The pattern and presentation of maxillofacial fractures had been studied in many parts of the world with varying results. Severe multiple trauma patients had different patterns of maxillofacial injuries. The number of maxillofacial trauma is on the rise worldwide as well as the incidence of associated sequelae. Maxillofacial fractures on multiple trauma patients were more frequent among males and in road traffic crashes. Knowing such data is elementary. The society should have a key role in the awareness of individuals and in prevention of road traffic accidents.

É alta a incidência de traumas na face. Este estudo teve por objetivo documentar e catalogar as fraturas maxilofaciais em pacientes com politraumatismos. De um total de 1229 casos de politraumatizados tratados na Sala de Emergência do Hospital de Santo António - Centro Hospitalar do Porto, Portugal, entre Agosto de 2001 e Dezembro de 2007, 251 pacientes tiveram ferimentos na face e 209 apresentaram fraturas maxilofaciais. As idades variaram de 13 a 86 anos. O método de seleção baseou-se na presença de ferimentos na face com Abreviated Injury Scale ≥1. Os homens apresentaram maior incidência de fraturas maxilofaciais (86,6%) entre os pacientes com múltiplos traumatismos na face e os acidentes de trânsito foram a causa principal dos traumatismos (69,38%). A região mais afetada foi o complexo naso-órbito-etmoidal (67,46%), seguido pela maxila (57,42%). O padrão e a apresentação das fraturas maxilofaciais tem sido estudado em muitas regiões do mundo com resultados variados. Pacientes com politraumatizados graves apresentaram padrões diferentes de traumatismos maxilofaciais. O número de traumatismos maxilofaciais tem aumentado à escala mundial, assim como a incidência das sequelas associadas. Entre os pacientes com traumatismos múltiplos, a maioria pertencia ao sexo masculino, assim como a causa mais frequente foram os acidentes automobilísticos. É elementar o conhecimento destes dados. A sociedade tem um papel primordial nos cuidados individuais e na prevenção dos acidentes de trânsito.

Envolvimento de receptores 5-HT2C do hipocampo ventral em comportamentos de defesa de ratos no labirinto em cruz elevado / Involvement of ventral hippocampus 5-HT2C receptors on defensive behaviors of rats in the elevated plus-maze

A ativação farmacológica dos receptores 5-HT2C induz comportamentos de defesa em modelos animais. O estudo busca investigar se o bloqueio seletivo de receptores 5-HT2C no hipocampo ventral (HV) previne comportamentos defensivos induzidos por um agonista de receptor 5-HT2C administrado perifericamente em ratos expostos ao labirinto em cruz elevado (LCE). Quinze minutos após injeções intraperitoniais (IP, 1ml/kg) do agonista 5-HT2C WAY-161503, ratos foram microinjetados bilateralmente no HV com o antagonista seletivo de receptores 5-HT2C SB-242084 (0, 0,1, 0,5 ou 1.5μg). Dez minutos após, cada animal foi exposto ao LCE para o registro de categorias de ansiedade. Injeções sistêmicas do WAY-161503 reduziram seletivamente as explorações nos braços abertos e aumentaram padrões de avaliação de risco. Esse efeito foi atenuado de maneira dose-dependente pela microinjeção de SB-242084 no HV, confirmando a ação ansiogênica de agonistas 5-HT2C e sugerindo que esse perfil comportamental seja mediado, pelo menos em parte, por receptores 5-HT2C do HV.

Pharmacological 5-HT2C receptor activation induces defensive behaviors in several animal models of anxiety. The present study investigated whether the selective blockade of 5-HT2C receptors in the ventral hippocampus (VH) prevents defensive behaviors induced by a 5-HT2C agonist administered systemically in rats exposed to the elevated plus-maze (EPM). Fifteen minutes after intraperitonial (IP, 1ml/kg) injections of the selective 5-HT2C receptor agonist WAY-161503 (3 mg/kg), rats were bilaterally microinjected with the selective 5-HT2C antagonist SB-242084 (0, 0.1, 0.5 or 1.5μg) into the VH. Ten minutes after, each animal was exposed to the EPM for measuring classical and ethological anxiety measures. IP WAY-161503 injections selectively decreased open-arm exploration while increasing risk-assessment. This anxiogenic-like action was dose-dependently attenuated by intra-VH SB-242084 microinjections. These results not only further confirm the anxiogenic-like action of 5-HT2C agonists, but also suggest that this behavioral profile might be mediated at least in part by VH 5-HT2C receptors.

The Drosophila melanogaster circadian pacemaker circuit.

As an experimental model system, the fruit fly Drosophila melanogaster has been seminal in shaping our understanding of the circadian clockwork. The wealth of genetic tools at our disposal over the past four decades has enabled discovery of the genetic and molecular bases of circadian rhythmicity. More recently, detailed investigation leading to the anatomical, neurochemical and electrophysiological characterization of the various neuronal subgroups that comprise the circadian machinery has revealed pathways through which these neurons come together to act as a neuronal circuit. Thus the D. melanogaster circadian pacemaker circuit presents a relatively simple and attractive model for the study of neuronal circuits and their functions.

Modulation of serum cortisol by substance P in albino rats: evidence of a direct effect on adrenal gland.

Effect of prolonged administration of substance P on the plasma cortisol level in the albino rats has been investigated. An inhibitory impact on intact individuals and a stimulatory effect in pharmacologically annulled rats has been observed. It is concluded that in normal conditions substance P presumably acts as a preventive agent for any excess secretion of cortisol while during stress or disturbed HPA or RAS conditions, it stimulates the secretion of cortisol. An intraglandular modulatory role of substance P has been suggested.

Neuromodulatory effects of caffeine and bromazepam on visual event-related potential (P300): a comparative study

O componente P300 do potencial evocado relacionado a evento é uma medida geral de "eficiência cognitiva" e um índice da qualidade do processamento e armazenamento de informações pelo sistema nervoso central (SNC). OBJETIVO: Comparar os efeitos neuromoduladores da cafeína e do bromazepam a partir do banco normativo do potencial evocado visual (P300). MÉTODO: 15 sujeitos destros (7 homens e 8 mulheres), entre 20 e 30 anos de idade, sadios, livres de qualquer déficit cognitivo e sem uso de substâncias psicotrópicas ou psicoativas foram estudados. Os sujeitos foram submetidos a uma tarefa de discriminação visual utilizando o paradigma "oddball", após a administração de uma cápsula de cafeína ou de bromazepam, em um desenho duplo-cego randomizado. RESULTADOS: Foram observadas diferenças estatisticamente significativas quando as condições cafeína e bromazepam foram comparadas com o banco normativo. CONCLUSÃO: Os resultados sugerem que a cafeína e o bromazepam têm efeitos moduladores específicos no SNC.

Gap junction modulation by extracellular signaling molecules: the thymus model

Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC) can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control

Reatividade vascular da artéria mamária interna: estudos farmacológicos comparativos entre artérias caninas direita e esquerda / Vascular reactivity of the internal mammary artery: comparative pharmacological studies between canine right and left arteries

Para estudos comparativos da reatividade vascular entre artéria mamária interna (AMI) canina direita e esquerda, realizaram-se experimentos "in vitro" utilizando-se banhos orgânicos ("organ chambers") e ensaios biológicos: 1) os produtos plaquetários ADP e 5-HT induziram, respectivamente, vasodilatação dependente e independente do endotélio; 2) os autacóides, bradicinina e histamina, também induziram vasodilatação, respectivamente, dependente e independente do endotélio; 3) o A23187, vasodilatador independente de receptor, induziu relaxamentos dependentes do endotélio; 4) dopamina, dobutamina, papaverina e a poli-L-arginina induziram vasodilatações independentes do endotélio; 5) a NOR induziu intensa vasoconstrição comparável à causada pelo KCI e pela endotelina; 6) em 83 porcento de 24 ensaios, a liberação basal de NO foi maior na AMI esquerda, em comparação com a AMI direita; 7) ensaios biológicos de AMIs demonstraram a importância da PGI2 nas condições de hipóxia, uma vez que a indometacina aboliu vasodilatação adicional em resposta à hipóxia em condições de vasodilatação induzida pela liberação basal de NO; 8) não ocorreram diferenças significantes de resposta, comparando-se estudos realizados em AMIs direita e esquerda

Zinc and water intake in rats: investigation of adrenergic and opiatergic central mechanisms

We have demonstrated that central administration of zinc in minute amounts induces a significant antidipsogenic action in dehydrated rats as well as in rats under central cholinergic and angiotensinergic stimulation. Here we show that acute third ventricle injections of zinc also block water intake induced by central ß-adrenergic stimulation in Wistar rats (190-250 g). Central inhibition of opioid pathways by naloxone reverses the zinc-induced antidipsogenic effect in dehydrated rats. After 120 min, rats receiving third ventricle injections of isoproterenol (160 nmol/rat) exhibited a significant increase in water intake (5.78 ± 0.54 ml/100 g body weight) compared to saline-treated controls (0.15 ± 0.07 ml/100 g body weight). Pretreatment with zinc (3.0, 30.0 and 300.0 pmol/rat, 45 min before isoproterenol injection) blocked water intake in a dose-dependent way. At the highest dose employed a complete blockade was demonstrable (0.54 ± 0.2 ml/100 g body weight). After 120 min, control (NaAc-treated) dehydrated rats, as expected, exhibited a high water intake (7.36 ± 0.39 ml/100 g body weight). Central administration of zinc blocked this response (2.5 ± 0.77 ml/100 g body weight). Naloxone pretreatment (82.5 nmol/rat, 30 min before zinc administration) reverted the water intake to the high levels observed in zinc-free dehydrated animals (7.04 ± 0.56 ml/100 g body weight). These data indicate that zinc is able to block water intake induced by central ß-adrenergic stimulation and that zinc-induced blockade of water intake in dehydrated rats may be, at least in part, due to stimulation of central opioid peptides

Central modulation of formalin-induced acute peripheral inflammation & pain by some putative amino acid neurotransmitters in rats.

Possible central modulation of acute peripheral inflammation by putative amino acid neurotransmitters was investigated in rats by adopting formalin induced pedal inflammation as an experimental model. Out of five amino acids (GABA, glycine, DL-alanine, L-glutamic acid and L-aspartic acid) tested, intracerebroventricular (icv) administration of GABA and L-aspartic acid produced significant alteration in acute inflammation. GABA showed a significant attenuation of paw oedema and nociception whereas, L-aspartic acid produced significant increase in oedema volume along with marked hyperalgesia. In conclusion, the study confirms that CNS is capable of modulating peripheral inflammation.

Bovine serum albumin potentiates caffeine - or ATP - induced tension in human skinned skeletal muscle fibers

Human skinned muscle fibers were used to investigate the effects of bovine serum albumin (BSA) on the tension/pCa relationship and on the functional properties of the Ca2+- release channel of the sarcoplasmic reticulum (SR). In both fast-and slow-type fibers, identified by their tension response to pSr 5.0, BSA (0.7-15 muM) had no effect on the Ca2+ affinity of the contractile proteins and elicited no tension per se in Ca2+-loaded fibers. In contrast, BSA (>1.0 muM) potentiated the caffeine induced tension in Ca2+-loaded fibers, this effect being more intense in slow-type fibers. Thus, BSA reduced the threshold caffeine concentration required for eliciting detectable tension, and increased the amplitude, the rate of rise and the area under the curve of caffeine-induced tension BSA also potentiated the tension elicited in Ca2+-loaded fibers by low-Mg2+ solutions containing 1.0 mM free ATP. These results suggest that BSA modulates the response of the human skeletal muscle SR Ca2+-release channel to activators such as caffeine and ATP.

Encefalitis equina venezolana: revisión / Venezuelan equine encephalomyelitis: review

La encefalomielitis equina venezolana (EEV) es una de las infecciones virales del sistema nervioso más serias, ya que tiene una rápida y amplia distribución geográfica y hasta puede producir secuelas como retardo mental, demencia, amnesia, aborto, epilepsia e hidroanencefalia en humanos y animales infectados. Esta infección se localiza principalmente en dos tejidos: linfohematopoyético y nervioso. El virus de la EEV tiene una especial actividad citopática sobre las células nerviosas (glía y neuronas) mientras que las lesiones que produce en la mielina probablemente son una consecuencia de la respuesta inmune del huesped. Las alteraciones producidas por el virus de la EEV en los diferentes tipos neuronales, pueden dar origen a modificaciones en las concentracions de diversos neurotransmisores y sus receptores localizados en la membrana plasmática. Otros cambios bioquímicos reportados parecen ser debidos al efecto citopático del virus

Thalamic ventrobasal stimulation for pain relief: probable mechanisms, pathways and neurotransmitters

A estimulaçäo talâmica ventrobasal (VB), primeiramente realizada por Mazars em 1961, é método útil para o tratamento de dor central e dor de deaferentaçäo. A maneira como ela atua para produzir alívio da dor, porém é ainda questäo de controvérdia. Neste estudo, o autor examina as hipóteses anteriormente propostas e sugere que o alívio da dor obtido pela estimulaçäo de VB se deve a dois prováveis mecanismos: (1) Modulaçäo da atividade anormal em VB e (2) Ativaçäo de uma via multisináptica inibitória para os neurônios nociceptivos do tálamo meidal, na qual o sistema dopaminérgico nigroestriatal exerce importante papel. A via multisináptica envolvida, bem como os neurotransmissores, säo sugeridos: a estimulaçäo de VB, através da via tálamo-corticalglutaminérgica, excitaria o córtex somatosensitivo que, por sua vez, excitaria o córtex motor através dos neurotransmissores excitatórios glutamato e aspartato. No córtex sensitivo-motor se originaria a via corticoestriatal glutaminérgica excitatória para o putâmen anterior, o qual emitiria uma via peptidérgica (substância P) excitatória para o globo pálido interno (via estiatopalidal) e para a substância nigra reticulata (via estriatonigral). O globo pálido interno inibiria o tálamo medial através da via pálido-talâmica gabaérgica. A substância nigra reticulata emitiria projeçöes gabaérgicas inibitórias para o tálamo medial (via nigrotalâmica) e excitaria a substância nigra compacta. A substância nigra compacta projetaria axônios dopaminérgicos excitatórios para os neurônios estriatais com eferência para o globo pálido interno e substância nigra reticulata e assim por diante. Dados de suporte a esta hipótese säo providos por extensa revisäo da literatura

Teorias aminérgicas da depressäo

Revisa-se os conceitos mais recentes em relaçäo às teorias aminérgicas da depressäo. Verifica-se que as teorias propostas no início da década de 60 sofreram certas modificaçöes contextuais. Em primeiro lugar, deixou de se dar ênfase a uma alteraçäo isolada como causa dos sintomas depressivos, pela constataçäo de que, in vivo, a variaç äo na disponibilidade de um neurotransmissor também influi na disstribuiçäo e metabolismo dos demais. Em segundo, passou-se a valorizar a contribuiçäo dos receptores pré e pós-sinápticos das aminas cerebrais, responsabilizando-os pelo prazo de latência necessários aos efeitos terapêuticos dos antidepressores em geral. As alteraç öes na sensibilidade e número desses receptores têm sido amplamente estudadas, porém resultados controversos näo permitiram correlaç äo clínica até o presente