Does L-carnitine prevent cadmium-induced damage in gastrointestinal contractility and histological changes in prepubertal rat / ¿La L-carnitina previene el daño inducido por cadmio en la contractilidad gastrointestinal y los cambios histológicos en ratas prepúberes?

SUMMARY: Cadmium (Cd) is the industrial and environmental toxic heavy metal which is found in air, water and soil. Cd, adversely affects many organs in humans such as kidney, intestine, liver, testis and lungs. L-carnitine (LC) is an important agent that plays essential role in energy metabolism. In our study, we aimed to work out whether LC application has any protective effect on intestinal contractility and morphologic damage of prepubertal rat duodenum on Cd-induced toxicity. Twenty eight prepubertal female Wistar rats were divided into four groups. The first group is control (C), second group; Cd group; Cadmium chloride was given 2 mg/kg 28 days with a one-day break by i.p. The third group; Cd+LC, which cadmium chloride was given 2 mg/kg i.p. and LC was given orally by gastric lavage. The LC dose was given as 75 mg/kg. The fourth group; LC, which only LC was given orally. The intestinal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (ACh) and relaxation was achieved with phenylephrine. Also the segments were examined for histological changes by light microscopy. Ach-induced contractions were higher in Cd+LC, LC, and control group compared to the Cd group in duodenal segments. The phenylephrine-induced relaxations were lower in Cd groups as compared with Control, Cd+LC and LC group in duodenal segments. In Cd group intestinal morphology was observed to be severely damaged whereas in Cd+LC group the damage was noticeably lower. Cd administration caused severe cellular damage and decreased gastrointestinal motility. Treatment with the LC has affected the gastrointestinal contractility and reduced the damage in intestinal morphology, which occured after Cd application.

El cadmio (Cd) es el metal pesado tóxico industrial y ambiental que se encuentra en el aire, el agua y el suelo. El Cd afecta negativamente a muchos órganos humanos, como los riñones, los intestinos, el hígado, los testículos y los pulmones. La L-carnitina (LC) es un agente importante que juega un rol esencial en el metabolismo energético. El objetivo de este estudio fue determinar si la aplicación de LC tiene algún efecto protector sobre la contractilidad intestinal y el daño morfológico del duodeno de rata prepuberal sobre la toxicidad inducida por Cd. Veintiocho ratas Wistar hembras prepúberes se dividieron en cuatro grupos. El primer grupo control (C), segundo grupo; grupo cd; Se administró cloruro de cadmio 2 mg/kg durante 28 días con un descanso de un día por vía i.p. El tercer grupo; Cd+LC, al que se administró cloruro de cadmio 2 mg/kg i.p. y LC se administró por vía oral mediante lavado gástrico. La dosis de LC se administró como 75 mg/kg. El cuarto grupo; LC, al cual solo LC se administraba por vía oral. Los segmentos intestinales fueron aislados y suspendieron en baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (ACh) y la relajación se logró con fenilefrina. También se examinaron los segmentos en busca de cambios histológicos mediante microscopía óptica. Las contracciones inducidas por Ach fueron mayores en Cd+LC, LC y el grupo control en comparación con el grupo Cd en los segmentos duodenales. Las relajaciones inducidas por fenilefrina fueron menores en los grupos Cd en comparación con el grupo Control, Cd+LC y LC en los segmentos duodenales. En el grupo Cd se observó que la morfología intestinal estaba severamente dañada mientras que en el grupo Cd+LC el daño fue notablemente menor. La administración de Cd causó daño celular severo y disminución de la motilidad gastrointestinal. El tratamiento con LC afectó la contractilidad gastrointestinal y redujo el daño en la morfología intestinal, que ocurría después de la aplicación de Cd.

Profile of malignant hyperthermia susceptibility reports confirmed with muscular contracture test in Brazil / Perfil dos relatos de suscetibilidade à hipertermia maligna confirmados com teste de contratura muscular no Brasil

Abstract Background and objectives: Malignant hyperthermia is an autosomal dominant hypermetabolic pharmacogenetic syndrome, with a mortality rate of 10%-20%, which is triggered by the use of halogenated inhaled anesthetics or muscle relaxant succinylcholine. The gold standard for suspected susceptibility to malignant hyperthermia is the in vitro muscle contracture test in response to halothane and caffeine. The determination of susceptibility in suspected families allows the planning of safe anesthesia without triggering agents for patients with known susceptibility to malignant hyperthermia by positive in vitro muscle contracture test. Moreover, the patient whose suspicion of malignant hyperthermia was excluded by the in vitro negative muscle contracture test may undergo standard anesthesia. Susceptibility to malignant hyperthermia has a variable manifestation ranging from an asymptomatic subject presenting a crisis of malignant hyperthermia during anesthesia with triggering agents to a patient with atrophy and muscle weakness due to central core myopathy. The aim of this study is to analyze the profile of reports of susceptibility to malignant hyperthermia confirmed with in vitro muscle contracture test. Method: Analysis of the medical records of patients with personal/family suspicion of malignant hyperthermia investigated with in vitro muscle contracture test, after given written informed consent, between 1997 and 2010. Results: Of the 50 events that motivated the suspicion of malignant hyperthermia and family investigation (sample aged 27 ± 18 years, 52% men, 76% white), 64% were investigated for an anesthetic malignant hyperthermia crisis, with mortality rate of 25%. The most common signs of a malignant hyperthermia crisis were hyperthermia, tachycardia, and muscle stiffness. Susceptibility to malignant hyperthermia was confirmed in 79.4% of the 92 relatives investigated with the in vitro muscle contracture test. Conclusion: The crises of malignant hyperthermia resembled those described in other countries, but with frequency lower than that estimated in the country.

Resumo Justificativa e objetivo: Hipertermia maligna é uma síndrome farmacogenética hipermetabólica, autossômica dominante, com mortalidade entre 10%-20%, desencadeada por uso de anestésico inalatório halogenado ou relaxante muscular succinilcolina. O padrão-ouro para pesquisa de suscetibilidade à hipertermia maligna é o teste de contratura muscular in vitro em resposta ao halotano e à cafeína. A determinação da suscetibilidade nas famílias suspeitas permite planejar anestesias seguras sem agentes desencadeantes para os pacientes confirmados como suscetíveis à hipertermia maligna pelo teste de contratura muscular in vitro positivo. Além disso, o paciente no qual a suspeita de hipertermia maligna foi excluída pelo teste de contratura muscular in vitro negativo pode ser anestesiado de forma convencional. Suscetibilidade à hipertermia maligna tem manifestação variável, desde indivíduo assintomático que apresenta crise de hipertermia maligna durante anestesia com agentes desencadeantes, até paciente com atrofia e fraqueza muscular por miopatia central core disease. O objetivo deste trabalho é analisar o perfil dos relatos de suscetibilidade à hipertermia maligna confirmados com teste de contratura muscular in vitro. Método: Análise das fichas de notificação dos pacientes com suspeita pessoal/familiar de hipertermia maligna investigados com teste de contratura muscular in vitro, após assinatura do termo de consentimento, entre 1997-2010. Resultados: Dos 50 eventos que motivaram a suspeita de hipertermia maligna e a investigação familiar (amostra com 27 ± 18 anos, 52% homens, 76% brancos), 64% foram investigados por crise de hipertermia maligna anestésica, com mortalidade de 25%. Sinais mais comuns da crise de hipertermia maligna foram hipertermia, taquicardia e rigidez muscular. Suscetibilidade à hipertermia maligna foi confirmada em 79,4% dos 92 parentes investigados com teste de contratura muscular in vitro. Conclusão: Crises de hipertermia maligna assemelharam-se às descritas em outros países, porém com frequência inferior à estimada no país.

Basil, tea tree and clove essential oils as analgesics and anaesthetics in Amphiprion clarkii (Bennett, 1830) / Óleos essenciais de manjericão, melaleuca e cravo como anestésicos e analgésicos em Amphiprion clarkii (Bennett, 1830)

Abstract In this study were evaluated the anaesthesia and analgesic effects of clove Eugenia caryophyllata, tea tree Melaleuca alternifolia and basil Ocimum basilicum essential oils (EO) during handling of yellowtail clownfish Amphiprion clarkii. Juveniles (3.70 ± 0.75 cm and 1.03 ± 0.50 g; mean ± standard deviation) were submitted to concentrations of 40, 50, 60, 70 and 80 µl L-1 of clove, 150, 200, 250, 300 and 350 µl L-1 of basil and 200, 300, 400, 500 and 600 µl L-1 of tea tree oils (n=10/concentration), previously defined in pilot tests. Individually and only once, fish from each treatment were placed in a glass recipient containing 1 L of seawater at a temperature of 25 °C, salinity of 35 g L-1 and the specific concentration of diluted EO (stock solution). Control (only seawater) and blank (seawater and ethanol at the highest concentration used to dilute the oils) treatments were also conducted. After reaching the stage of surgical anaesthesia, fish were submitted to biometry and a sensibility test. After that, they were transferred to clean seawater for anaesthesia recovery. The times of induction needed to reach each anaesthesia stage and anaesthesia recovery were recorded. Animals were observed for 72 hours after the procedures. All the EO provoked anaesthesia and analgesic effects in A. clarkii, but basil oil is not recommended because it caused involuntary muscle contractions and mortality in 100% and 12% of fish, respectively. The lower concentrations that promote suitable induction and recovery times are 50 µl L-1 of clove oil and 500 µl L-1 of tea tree oil. However, due to its complementary high analgesic efficiency, clove oil is recommended as the ideal anaesthetic for A. clarkii.

Resumo Neste estudo foram avaliados os efeitos anestésicos e analgésicos dos óleos essenciais (OE) de cravo Eugenia caryophyllata, melaleuca Melaleuca alternifolia e manjericão Ocimum basilicum durante manejo de peixes-palhaços Amphiprion clarkii. Juvenis (3.70 ± 0.75 cm e 1.03 ± 0.50 g; média ± desvio padrão) foram submetidos às concentrações de 40, 50, 60, 70 e 80 µl L-1 de cravo, 150, 200, 250, 300 e 350 µl L-1 de manjericão e 200, 300, 400, 500 e 600 µl L-1 de melaleuca (n=10/concentração), previamente definidas em testes pilotos. Individualmente e somente uma vez, os peixes de cada tratamento foram colocados em recipiente de vidro contendo 1 L de água salgada, em temperatura de 25 °C, salinidade de 35 g L-1 e a concentração específica de OE diluída (solução estoque). Tratamentos controle (apenas água marinha) e branco (água marinha e a maior concentração de etanol utilizada para diluição dos óleos) também foram conduzidos. Após atingirem o estágio de anestesia cirúrgica, os peixes foram submetidos à biometria e teste de sensibilidade. Em seguida, foram transferidos para água marinha limpa. Os tempos necessários para atingir cada estágio anestésico e recuperação foram registrados. Os animais foram observados por 72 horas após os procedimentos. Todos os OE provocaram anestesia e analgesia em A. clarkii, porém o óleo de manjericão não é recomendado, pois causou contrações musculares involuntárias e mortalidade em 100% e 12% dos animais, respectivamente. As menores concentrações que promovem indução anestésica e recuperação em tempos adequados são 50 µl L-1 de óleo de cravo e 500 µl L-1 de óleo de melaleuca. Entretanto, devido à sua alta eficiência analgésica complementar, o óleo de cravo é recomendado como o anestésico ideal para A. clarkii.

Effects of nitric oxide inhibitors in mice with bladder outlet obstruction

ABSTRACT Purpose To investigate the lower urinary tract changes in mice treated with L-NAME, a non-selective competitive inhibitor of nitric oxide synthase (NOS), or aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS), after 5 weeks of partial bladder outlet obstruction (BOO), in order to evaluate the role of constitutive and non-constitutive NOS in the pathogenesis of this experimental condition. Materials and Methods C57BL6 male mice were partially obstructed and randomly allocated into 6 groups: Sham, Sham + L-NAME, Sham + aminoguanidine, BOO, BOO + L-NAME and BOO + aminoguanidine. After 5 weeks, bladder weight was obtained and cystometry and tissue bath contractile studies were performed. Results BOO animals showed increase of non-voiding contractions (NVC) and bladder capacity, and also less contractile response to Carbachol and Electric Field Stimulation. Inhibition of NOS isoforms improved bladder capacity and compliance in BOO animals. L-NAME caused more NVC, prevented bladder weight gain and leaded to augmented contractile responses at muscarinic and electric stimulation. Aminoguanidine diminished NVC, but did not avoid bladder weight gain in BOO animals and did not improve contractile responses. Conclusion It can be hypothesized that chronic inhibition of three NOS isoforms in BOO animals leaded to worsening of bladder function, while selective inhibition of iNOS did not improve responses, what suggests that, in BOO animals, alterations are related to constitutive NOS.

Temblores posanestésicos / Post-anesthetic shivering

Introducción: los temblores posanestésico son causa de una de las mayores insatisfacciones durante el posoperatorio inmediato. Es un fenómeno frecuente, potencialmente perjudicial por aumentar la demanda metabólica de oxígeno. Objetivo: hacer una actualización sobre los temblores Posanestésicos y su profilaxis. Métodos: constituyen una actividad muscular oscilatoria para aumentar la producción de calor. Su etiología es desconocida, aunque se le atribuyen numerosas causas. Su frecuencia oscila entre 6,3 y 66 por ciento. De 5 a 65 por ciento relacionadas con anestesia general y 30 por ciento con anestesia regional. Con anestesia general, la temperatura central disminuye entre 0,5 y 1,5 °C, en la primera hora posterior a la inducción, al igual que en la anestesia regional. Este mecanismo se produce por redistribución del calor del centro a la periferia. Todos los anestésicos, opioides y sedantes disminuyen la vasoconstricción y el control autonómico de la regulación térmica y facilitan la hipotermia. Se presenta con mayor frecuencia en pacientes jóvenes, del sexo masculino, en los cuales se administraron agentes anestésicos halogenados, con tiempo anestésico quirúrgico prolongado. Numerosos artículos señalan, que en las especies homeotérmicas se presenta un sistema termorregulador que coordina la defensa contra la temperatura ambiental, para mantener la temperatura interna en un umbral estrecho. La combinación de agentes inductores anestésicos y exposición al ambiente frío hacen que los pacientes presenten temblores posanestésicos. Su profilaxis está dada por el uso de meperidina, clonidina y tramadol. La ketamina, es una fenciclidina, que produce disociación electrofisiológica entre los sistemas límbico y cortical. Se une a dos dianas moleculares en el encéfalo: las terminaciones dopaminérgicas en el núcleo accumbens y los receptores de N-metil de aspartato. Cuando la ketamina se une a dichos receptores, inhibe la liberación de dopamina. Conclusiones: los temblores Posanestésicos constituyen un efecto adverso de la anestesia que pueden ser evitados. La ketamina, por su mecanismo de acción parece jugar un papel en su profilaxis, pues al bloquear dicho receptor se infiere que es posible que module, en alguna medida, la regulación térmica en varios niveles(AU)

Introduction: post-anesthetic shivering is caused by one of the greatest dissatisfactions during the immediate postoperative period. It is a common event, also potentially damaging because it increases the metabolic demand for oxygen. Objective: To make an update on post-anesthetic shivering and its prophylaxis. Methods: It constitutes an oscillatory muscle activity to increase heat production. Its etiology is unknown, although it is attributed to many causes. Its frequency varies between 6.3 and 66 percent. 5 to 65 percent are related to general anesthesia, and 30 percent to regional anesthesia. Under general anesthesia, the central temperature decreases from 0.5 to 1.5 °C in the first hour after induction, as in regional anesthesia. This mechanism is caused by redistribution of heat from the center to the periphery. All anesthetics, opioids and sedatives decrease vasoconstriction and the autonomic control of thermal regulation, and facilitate hypothermia. It occurs most often in young patients, male, to whom halogenated anesthetic agents are administered with anesthetic prolonged surgical time. Many items indicate that in the homeothermic species a thermoregulator system is present, which coordinates the defense against the environmental temperature to maintain the internal temperature in a narrow threshold. The combination of anesthetic inducing agents and exposure to cold environment make patients present post-anesthetic shivering. Prophylaxis is attained by using meperidine, clonidine and tramadol. Ketamine is a phencyclidine, which produces electrophysiological dissociation between the limbic and cortical systems. It is bound to two molecular targets in the brain: dopaminergic terminals in the accumbens nucleus and the N-methyl aspartate receptor. When ketamine binds to these receptors, it inhibits the release of dopamine. Conclusions: Post-anesthetic shivering constitutes an adverse effect of anesthesia, which can be avoided. Ketamine, for its action mechanism, seem to play a role in prevention, because when such receptor is blocked, it is inferred to module, at some extent, thermal regulation at various levels(AU)

Effect of S-methyl-l-thiocitrulline dihydrochloride on rat micturition reflex

ABSTRACT Objective: To evaluate the effect of neuronal nitric oxide synthase on the striated urethral sphincter and the urinary bladder. Materials and Methods: A coaxial catheter was implanted in the proximal urethra and another one in the bladder of female rats, which were anesthetized with subcutaneous injection of urethane. The urethral pressure with saline continuous infusion and bladder isovolumetric pressure were simultaneously recorded. Two groups of rats were formed. In group I, an intrathecal catheter was implanted on the day of the experiment at the L6-S1 level of the spinal cord; in group II, an intracerebroventricular cannula was placed 5-6 days before the experiment. Results: It was verified that the group treated with S-methyl-L-thio-citrulline, via intrathecal pathway, showed complete or partial inhibition of the urethral sphincter relaxation and total inhibition of the micturition reflexes. The urethral sphincter and the detrusor functions were recovered after L-Arginine administration. When S-methyl-L-thio-citrulline was administered via intracerebroventricular injection, there was a significant increase of urethral sphincter tonus while preserving the sphincter relaxation and the detrusor contractions, at similar levels as before the use of the drugs. Nevertheless there was normalization of the urethral tonus when L-Arginine was applied. Conclusions: The results indicate that, in female rats anaesthetized with urethane, the nNOS inhibitor administrated through the intrathecal route inhibits urethral sphincter relaxation, while intracerebroventricular injection increases the sphincter tonus, without changing bladder function. These changes were reverted by L-Arginine administration. These findings suggest that the urethral sphincter and detrusor muscle function is modulated by nitric oxide.

ß-Citronellol, an alcoholic monoterpene with inhibitory properties on the contractility of rat trachea

β-Citronellol is an alcoholic monoterpene found in essential oils such Cymbopogon citratus (a plant with antihypertensive properties). β-Citronellol can act against pathogenic microorganisms that affect airways and, in virtue of the popular use of β-citronellol-enriched essential oils in aromatherapy, we assessed its pharmacologic effects on the contractility of rat trachea. Contractions of isolated tracheal rings were recorded isometrically through a force transducer connected to a data-acquisition device. β-Citronellol relaxed sustained contractions induced by acetylcholine or high extracellular potassium, but half-maximal inhibitory concentrations (IC50) for K+-elicited stimuli were smaller than those for cholinergic contractions. It also inhibited contractions induced by electrical field stimulation or sodium orthovanadate with pharmacologic potency equivalent to that seen against acetylcholine-induced contractions. When contractions were evoked by selective recruitment of Ca2+ from the extracellular medium, β-citronellol preferentially inhibited contractions that involved voltage-operated (but not receptor-operated) pathways. β-Citronellol (but not verapamil) inhibited contractions induced by restoration of external Ca2+ levels after depleting internal Ca2+ stores with the concomitant presence of thapsigargin and recurrent challenge with acetylcholine. Treatment of tracheal rings with L-NAME, indomethacin or tetraethylammonium did not change the relaxing effects of β-citronellol. Inhibition of transient receptor potential vanilloid subtype 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1) receptors with selective antagonists caused no change in the effects of β-citronellol. In conclusion, β-citronellol exerted inhibitory effects on rat tracheal rings, with predominant effects on contractions that recruit Ca2+ inflow towards the cytosol by voltage-gated pathways, whereas it appears less active against contractions elicited by receptor-operated Ca2+ channels.

Enhanced cyclooxygenase-2 activity leads to intestinal dysmotility following hemorrhagic shock

ABSTRACT PURPOSE: To test whether hemorrhagic shock (HS) increases the Cyclooxygenase-2 (COX-2) expression in the intestine and whether this enhanced COX-2 expression mediates the intestinal dysmotility after HS. METHODS: Male Wistar rats were randomly divided into HS sham group and HS group. At 180 min following HS establishment, the duodenum samples were harvested to assess the motility function, protein expression of COX-2 and the downstream products of COX-2, prostaglandins. RESULTS: Examination of motility function ex vivo showed that the contractile response to acetylcholine of smooth muscle strips of rats subjected to HS was significantly suppressed. A COX-2 inhibitor, NS-398, abolished this depressed contractile response after HS. Western blotting revealed an increased protein expression of COX-2 in intestinal tissues of HS rats. Immunohistochemical examination indicated that intestine tissues of HS rats were manifested by part of villous expansion and disruption, a large amount of COX-2 positive cells appearance in lamina propria and submucosa. Furthermore, the contents of prostaglandin E2 was significantly increased in intestinal tissues of HS rats. CONCLUSION: The enhanced COX-2/ prostaglandin E2 involves in the hemorrhagic shock induced intestinal dysmotility.

Functional and biochemical characteristics of urinary bladder muscarinic receptors in long-term alloxan diabetic rats / Características funcionais e bioquímicas dos receptores muscarínicos da bexiga de ratos com diabetes crônico induzido por aloxana

Objective To re-examine the function of the urinary bladder in vivoas well as to determine the functional and biochemical characteristics of bladder muscarinic receptors in long-term alloxan-induced diabetes rats.Methods Two-month-old male Wistar rats were injected with alloxan and the animals showing blood glucose levels >300mg/dL together with age-paired untreated animals were kept for 11 months. Body weight, bladder weight, blood glucose, and urinary volume over a period of 24 hours were determined in both groups of animals. A voiding cystometry in conscious control and diabetic rats was performed to determine maximal micturition pressure, micturition contraction interval and duration as well as voided and post-voiding residual volume. In addition, concentration-response curves for bethanechol in isolated bladder strips, as well as [3H]-N methyl-scopolamine binding site characteristics in bladder homogenates were determined.Results Mean bladder weight was 162.5±21.2mg versus 290±37.9mg in control and treated animals, respectively (p<0.05). Micturition contraction amplitude (34.6±4.7mmHg versus 49.6±2.5mmHg), duration (14.5±1.7 seconds versus 23.33±4.6 seconds) and interval (87.5±17.02 seconds versus 281.11±20.24 seconds) were significantly greater in alloxan diabetic rats. Voided urine volume per micturition contraction was also significantly higher in diabetic animals. However the post-voiding residual volume was not statistically different. Bethanechol potency (EC50 3µM versus 5µM) and maximal effect (31.2±5.9g/g versus 36.1±6.8g/g) in isolated bladder strips as well as number (169±4fmol/mg versus 176±3fmol/mg protein) and affinity (0.69±0.1nM versus 0.57±0.1nM) of bladder muscarinic receptors were also not statistically different.Conclusion Bladder function in vivo is altered in chronic alloxan-induced diabetes rats without changes in functional and biochemical characteristics of bladder muscarinic receptors.

Objetivo Reestudar o funcionamento da bexiga in vivo e determinar as características funcionais e bioquímicas dos receptores muscarínicos vesicais de ratos com diabetes crônico induzido por aloxana.Métodos Ratos Wistar de dois meses de idade receberam injeção de aloxana, e os animais que apresentaram glicemia >300mg/dL foram mantidos por 11 meses junto de outros não tratados e pareados por idade. Nos dois grupos de animais, peso corpóreo, peso da bexiga, glicemia e volume urinário de 24 horas foram medidos. Em ambos os grupos, realizou-se a cistometria miccional em animais não anestesiados. Foram determinados os seguintes parâmetros: pressão máxima de micção, intervalo e contração de micção, bem como o volume de esvaziamento e o volume residual pós-miccional. Além disso, foram determinadas as curvas de concentração-resposta a betanecol em preparações isoladas de bexiga e também as características dos sítios de ligação da [3H]-N-metil-escopolamina em homogenatos de bexiga.Resultados O peso médio da bexiga foi de 162,5±21,2mg versus290±37,9mg nos animais controles e tratados, respectivamente (p<0,05). A amplitude de contração (34,6±4,7mmHg versus 49,6±2,5mmHg), a duração (14,5±1,7 segundos versus 23,33±4,6 segundos) e o intervalo (87,5±17,02 segundos versus 281,11±20,24 segundos) de micção foram significantemente maiores nos ratos tratados com aloxana. O volume de urina eliminada durante a contração miccional também foi maior nos animais diabéticos. Contudo, o volume residual pós-miccional não foi estatisticamente diferente. Não foram observadas diferenças na resposta ao betanecol (EC50 3µM versus 5µM) e no seu efeito máximo (31,2±5,9g/g versus 36,1±6,8g/g) em preparações isoladas de bexiga, bem como no número total (169±43fmol/mgversus 176±3fmol/mg) e na afinidade (0,69±0,1nMversus 0,57±0,1nM) dos receptores muscarínicos da bexiga.Conclusão O funcionamento da bexiga in vivo está alterado no diabetes crônico induzido por aloxana, porém sem alterações funcionais e bioquímicas nos receptores muscarínicos da bexiga.

Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats / Efeitos de uma Sessão de Exercício Resistido sobre o Músculo Liso Vascular de Ratos Hipertensos

AbstractBackground:Hypertension is a public health problem and increases the incidence of cardiovascular diseases.Objective:To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats.Methods:Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP).Results:Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H.Conclusion:One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

ResumoFundamento:A hipertensão é um problema de saúde pública e faz aumentar a incidência das doenças cardiovasculares.Objetivo:Avaliar os efeitos de uma sessão de exercício resistido sobre os mecanismos contráteis e relaxantes do músculo liso vascular em artéria mesentérica de ratos hipertensos induzidos por L-NAME.Métodos:Ratos Wistar foram divididos em três grupos: Controle (C), Hipertenso (H) e Hipertenso Exercitado (HE). A hipertensão foi induzida pela administração de 20 mg/kg de NG-nitro L-arginina metil éster (L-NAME) durante sete dias antes dos protocolos experimentais. O protocolo de exercício resistido consistiu em dez séries de dez repetições e intensidade de 40% de uma repetição máxima. A reatividade do músculo liso vascular foi avaliada através de curvas concentração-resposta para a fenilefrina (FEN), cloreto de potássio (KCl) e nitroprussiato de sódio (NPS).Resultados:Os ratos tratados com L-NAME apresentaram aumento (p < 0,001) da Pressão Arterial Sistólica (PAS), da Pressão Arterial Diastólica (PAD) e da Pressão Arterial Média (PAM) quando comparados ao período inicial da indução. Não foi observada diferença na sensibilidade da FEN entre os grupos H e HE. O exercício resistido agudo reduziu (p < 0,001) a resposta contrátil induzida pelo KCl nas concentrações de 40 e 60 mM do grupo HE quando comparado ao grupo H. Foi observado maior (p < 0,01) sensibilidade do músculo liso ao NPS no grupo HE quando comparado ao grupo H.Conclusão:Uma sessão de exercício resistido reduz as respostas contráteis induzidas pelo KCl, além de aumentar a sensibilidade do músculo liso ao NO em artéria mesentérica de ratos hipertensos.

Relaxant effects of a hydroalcoholic extract of Ruta graveolens on isolated rat tracheal rings

BACKGROUND: Ruta graveolens L. (R. graveolens) is a medicinal plant employed in non-traditional medicines that has various therapeutic properties, including anthelmintic, and vasodilatory actions, among others. We evaluated the trachea-relaxant effects of hydroalcoholic extract of R. graveolens against potassium chloride (KCl)- and carbachol-induced contraction of rat tracheal rings in an isolated organ bath. RESULTS: The results showed that the airway smooth muscle contraction induced by the depolarizing agent (KCl) and cholinergic agonist (carbachol) was markedly reduced by R. graveolens in a concentration-dependent manner, with maximum values of 109 ± 7.9 % and 118 ± 2.6 %, respectively (changes in tension expressed as positive percentages of change in proportion to maximum contraction), at the concentration of 45 µg/mL (half-maximal inhibitory concentration IC50: 35.5 µg/mL and 27.8 µg/mL for KCl- and carbachol-induced contraction, respectively). Additionally, the presence of R. graveolens produced rightward parallel displacement of carbachol dose-response curves and reduced over 35 % of the maximum smooth muscle contraction. CONCLUSIONS: The hydroalcoholic extract of R. graveolens exhibited relaxant activity on rat tracheal rings. The results suggest that the trachea-relaxant effect is mediated by a non-competitive antagonistic mechanism. More detailed studies are needed to identify the target of the inhibition, and to determine more precisely the pharmacological mechanisms involved in the observed biological effects.

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.

Calendario de inicio sexual en México: Comparación entre encuestas nacionales y tendencias en el tiempo / Sexual debut in Mexico: a comparison of household national surveys

Objetivo. Estimar el calendario de inicio sexual en México y sus tendencias a partir de encuestas poblacionales. Material y métodos. Se analizaron cinco cohortes de nacimiento con cuatro encuestas nacionales (Encuesta Nacional de Salud 2000, Encuesta Nacional de la Dinámica Demográfica 2009, Encuesta Nacional de Juventud 2010 y Encuesta Nacional de Salud y Nutrición 2012) y se identificaron las proporciones de individuos que iniciaron actividad sexual antes de los 16 y antes de los 20 años. Resultados. Las distintas encuestas son, en general, consistentes, pero difieren entre ellas en algunas cohortes. En las cohortes más jóvenes, se identificó una proporción algo mayor de individuos que iniciaron antes de los 20 años; no se advierten cambios en el inicio sexual antes de los 16 años. Conclusiones. La falta de grandes cambios en la edad de inicio de vida sexual con tendencia al adelanto del calendario en México llama a fortalecer la educación sexual integral y la oferta de servicios de salud sexual y reproductiva accesibles a los adolescentes.

Objective. To estimate calendar of sexual debut in Mexico and its trends using national representative household surveys. Materials and methods. Analysis of five birth cohorts extracted from four national population based household surveys in Mexico (National Health Survey 2000, National Survey on Demographic Dynamics 2009, National Youth Survey 2010, and National Health & Nutrition Survey 2012), using as outcome the proportion of individuals that reported sexual debut before the age of 16 and before the age of 20. Results. Overall, the four analyzed surveys produce consistent results, although some differences were found. While a larger proportion among younger cohorts reported sexual debut before the age of 20, that was not the case for sexual debut before 16 years. Conclusions. While data seems to reflect a relative stable age of sexual debut in Mexico, there is a recent trend to prepone sexual initiation that highlights the need to strengthen comprehensive sexual education and the supply of sexual & reproductive health services that are accessible and friendly to adolescents thus responding to the growing demand from this age group.

Modulatory effects of taurine on jejunal contractility

Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

Cleansing the world of the germ of laziness: hygiene, sanitation, and the Javanese population in Suriname / Limpando o mundo do germe da preguiça: higiene, saneamento e população javanesa no Suriname

In 1915 the Rockefeller Foundation took its hookworm eradication campaign to Suriname, but was soon disappointed because of opposition from its main target group: the Javanese. Moreover, authorities and planters objected to the construction of latrines because of the costs and their belief that the Javanese were “unhygienic”. In describing the labor migration from Java to Suriname, I show that this “lack of hygiene” was closely related to the system’s organization. I argue that uncleanliness was the consequence of harmful socio-economic and ecological conditions. Secondly I suggest that even though the Foundation did not manage to cleanse Suriname of hookworm, its educational efforts, its emphasis on prevention, and its training of local health workers probably had more impact than Rockefeller officials thought.

Em 1915, a Fundação Rockefeller levou sua campanha de erradicação da ancilostomíase ao Suriname, logo sofrendo a oposição de seu principal alvo, os javaneses. Autoridades e proprietários rurais também reagiram à instalação de latrinas devido aos custos implicados e à crença de que os javaneses eram “anti-higiênicos”. Ao descrever a migração de trabalhadores de Java para o Suriname, mostro que a “falta de higiene” ligava-se à organização do sistema. Argumento que a sujeira era consequência de condições ecológicas e socioeconômicas danosas. Sugiro ainda que, embora a Fundação não tenha livrado o Suriname da anciolostomíase, seus esforços educacionais, sua ênfase na prevenção e o treinamento de profissionais de saúde locais tiveram maior impacto do que o imaginado pelos funcionários da agência norte-americana.

"The group facilitates everything": meanings patients with type 2 diabetes mellitus assigned to health education groups / "O grupo facilita tudo": significados atribuídos por pacientes portadores de diabetes mellitus tipo 2 a grupos de educação em saúde / "El grupo facilita todo": significados atribuidos por pacientes con diabetes mellitus tipo 2 a grupos de educación para la salud

OBJECTIVE: to interpret the meanings patients with type 2 diabetes mellitus assign to health education groups. METHOD: ethnographic study conducted with Hyperdia groups of a healthcare unit with 26 informants, with type 2 diabetes mellitus, and having participated in the groups for at least three years. Participant observation, social characterization, discussion groups and semi-structured interviews were used to collect data. Data were analyzed through the thematic coding technique. RESULTS: four thematic categories emerged: ease of access to the service and healthcare workers; guidance on diabetes; participation in groups and the experience of diabetes; and sharing knowledge and experiences. The most relevant aspect of this study is the social use the informants in relation to the Hyperdia groups under study. CONCLUSION: the studied groups are agents producing senses and meanings concerning the process of becoming ill and the means of social navigation within the official health system. We expect this study to contribute to the actions of healthcare workers coordinating these groups given the observation of the cultural universe of these individuals seeking professional care in the various public health care services. .

OBJETIVO: interpretar os significados atribuídos por pacientes portadores de diabetes mellitus tipo 2 a grupos de educação em saúde. MÉTODO: estudo etnográfico em cinco grupos Hiperdia de um centro de saúde, com 26 informantes portadores de diabetes mellitus tipo 2 que participavam dos grupos há, no mínimo, três anos. Para coligir as informações, utilizaram-se observação participante, caracterização social, grupos de discussão e entrevistas semiestruturadas. Os dados foram analisados por meio da técnica de codificação temática. RESULTADOS: emergiram quatro categorias temáticas - facilidades de acesso ao serviço e profissionais de saúde, orientações sobre o diabetes, participação nos grupos e experiência com o diabetes e compartilhamento de saberes e experiências. O aspecto mais relevante deste estudo diz respeito aos usos sociais que os informantes conferiam aos grupos Hiperdia pesquisados. CONCLUSÃO: os grupos estudados mostraram-se como instâncias produtoras de sentidos e de significados, concernentes ao processo de adoecimento e aos modos de navegação social no interior do sistema oficial de saúde. Almeja-se que este estudo possa contribuir para as ações dos profissionais de saúde que atuam nesses grupos, tendo em vista a observação do universo cultural dos indivíduos que procuram por cuidado profissional, nos diversos serviços públicos de saúde. .

OBJETIVO: interpretar los significados atribuidos por pacientes con diabetes mellitus tipo 2 a los grupos de educación para la salud. MÉTODO: estudio etnográfico en cinco grupos Hiperdia de un centro de salud, con 26 informantes con diabetes mellitus tipo 2 que participaban de los grupos hace, por lo menos, tres años. Para recolectar las informaciones se utilizaron la observación participante, la caracterización social, los grupos de discusión y las entrevistas semiestructuradas. Los datos fueron analizados por medio de la técnica de codificación temática. RESULTADOS: surgieron cuatro categorías temáticas: facilidades de acceso al servicio y profesionales de la salud; orientaciones sobre la diabetes; participación en los grupos y experiencia con la diabetes; y, compartir conocimientos y experiencias. El aspecto más relevante de este estudio se refiere a los usos sociales que los informantes daban a los grupos Hiperdia investigados. CONCLUSIÓN: los grupos estudiados se mostraron capaces de producir sentidos y significados concernientes al proceso de enfermarse y a los modos de navegación social en el interior del sistema oficial de salud. El objetivo de este estudio es que pueda contribuir para las acciones de los profesionales de la salud que actúan en esos grupos, considerando la observación del universo cultural de los individuos que buscan cuidados profesionales en los diversos servicios públicos de salud. .

Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels

After depletion of intracellular Ca2+ stores the capacitative response triggers an extracellular Ca2+ influx through store-operated channels (SOCs) which refills these stores. Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin- and histamine-induced contractions. Intracellular Ca2+ depletion by a Ca2+-free extracellular solution followed by Ca2+ readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate (2-APB), suggesting a capacitative response. In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one, likely because 2-APB inhibited store refilling by capacitative Ca2+ entry. 2-APB inhibition of sarcoplasmic reticulum Ca2+ release was excluded because this blocker did not affect serotonin force development in a Ca2+-free solution. The PCR technique showed the presence of mRNAs for STIM proteins (1 and 2), for Orai proteins (1, 2 and 3) and for TRPC channels (subtypes 1, 3, 4 and 6) in the smooth muscle of the human umbilical artery. Hence, this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.

Methionine Enhances the Contractile Activity of Human Colon Circular Smooth Muscle In Vitro

Effective drug to manage constipation has been unsatisfactory. We sought to determine whether methionine has effect on the human colon. Human colon tissues were obtained from the specimens of colon resection. Microelectrode recording was performed and contractile activity of muscle strips and the propagation of the contractions in the colon segment were measured. At 10 microM, methionine depolarized the resting membrane potential (RMP) of circular muscle (CM) cells. In the CM strip, methionine increased the amplitude and area under the curve (AUC) of contractions. In the whole segment of colon, methionine increased the amplitude and AUC of the high amplitude contractions in the CM. These effects on contraction were maximal at 10 microM and were not observed in longitudinal muscles in both the strip and the colon segment. Methionine reversed the effects of pretreatment with sodium nitroprusside, tetrodotoxin and Nw-oxide-L-arginine, resulting in depolarization of the RMP, and increased amplitude and AUC of contractions in the muscle strip. Methionine treatment affected the wave pattern of the colon segment by evoking small sized amplitude contractions superimposed on preexisting wave patterns. Our results indicate that a compound mimicking methionine may provide prokinetic functions in the human colon.

Sildenafil decreases rat tracheal hyperresponsiveness to carbachol and changes canonical transient receptor potential gene expression after antigen challenge

Inhibition of type-5 phosphodiesterase by sildenafil decreases capacitative Ca2+ entry mediated by transient receptor potential proteins (TRPs) in the pulmonary artery. These families of channels, especially the canonical TRP (TRPC) subfamily, may be involved in the development of bronchial hyperresponsiveness, a hallmark of asthma. In the present study, we evaluated i) the effects of sildenafil on tracheal rings of rats subjected to antigen challenge, ii) whether the extent of TRPC gene expression may be modified by antigen challenge, and iii) whether inhibition of type-5 phosphodiesterase (PDE5) may alter TRPC gene expression after antigen challenge. Sildenafil (0.1 µM to 0.6 mM) fully relaxed carbachol-induced contractions in isolated tracheal rings prepared from naive male Wistar rats (250-300 g) by activating the NO-cGMP-K+ channel pathway. Rats sensitized to antigen by intraperitoneal injections of ovalbumin were subjected to antigen challenge by ovalbumin inhalation, and their tracheal rings were used to study the effects of sildenafil, which more effectively inhibited contractions induced by either carbachol (10 µM) or extracellular Ca2+ restoration after thapsigargin (1 µM) treatment. Antigen challenge increased the expression of the TRPC1 and TRPC4 genes but not the expression of the TRPC5 and TRPC6 genes. Applied before the antigen challenge, sildenafil increased the gene expression, which was evaluated by RT-PCR, of TRPC1 and TRPC6, decreased TRPC5 expression, and was inert against TRPC4. Thus, we conclude that PDE5 inhibition is involved in the development of an airway hyperresponsive phenotype in rats after antigen challenge by altering TRPC gene expression.

Effects of marmin, a compound isolated from Aegle marmelos Correa, on contraction of the guinea pig-isolated trachea

Marmin or 7-[6', 7'-dihydroxygeranyl-oxy] coumarin is a compound isolated from Aegle marmelos Correa. In the study, we examined the effects of marmin on the contraction of guinea pig-isolated trachea stimulated by several inducers, namely histamine, metacholine, compound 48/80. We also evaluated its action against contraction induced by extracellular or intracellular calcium ion. The possibility of marmin to potentiate the

elaxation effect of isoprenaline was also studied. Marmin added in the organ bath at 10 min prior to the agonist inhibited the contraction elicited by histamine and metacholine in a concentration-dependent manner. Moreover, marmin antagonized the histamine-induced contraction in competitive manner. Marmin mildly potentiated the relaxation effect of isoprenaline. In the study, marmin abrogated the contraction of tracheal smooth muscle induced by compound 48/80, an inducer of histamine release. Besides, marmin successfully inhibited CaCl[2-]-induced contraction in Ca[2+] -free Krebs solution. Marmin also inhibited two phases of contraction which were consecutively induced by metacholine and CaCl[2] in Ca[2+]-free Krebs solution. Based on the results we concluded that marmin could inhibit contraction of the guinea-pig tracheal smooth muscle, especially by interfering histamine receptor, inhibiting the histamine release from mast, inhibiting intracellular Ca[2+] release from the intracellular store and the Ca[2+] influx through voltage-dependent Ca[2+] channels