Acetylcholine produces contractions mediated by the cyclooxygenase pathway in arterial vessels in the Chilean frog (Calyptocephalella gayi) / Acetilcolina produz contrações mediadas pela via da ciclooxigenase em vasos arteriais da rã chileno (Calyptocephalella gayi)

Abstract Previous studies performed in marine fish (I. conceptionis and G. laevifrons) showed that indomethacin blocked arterial contraction mediated by acetylcholine (ACh). The objective of this study was to determine if contraction induced by acetylcholine is mediated by the cyclooxygenase pathway in several arterial vessels in the Chilean frog Calyptocephalella gayi. Arteries from the pulmonary (PA), dorsal (DA), mesenteric (MA) and iliac (IA) regions were dissected from 6 adult specimens, and isometric tension studies were done using dose response curves (DRC) for ACh (10-13 to 10-3 M) in presence of a muscarinic antagonist (Atropine 10-5 M) and an unspecific inhibitor of cyclooxygenases (Indomethacin, 10-5M). All the studied arteries exhibited vasoconstriction mediated by ACh. This vasoconstriction was abolished in the presence of atropine in DA, MA and IA and attenuated in PA. Indomethacin abolished the vasoconstriction in MA and attenuated the response in PA, DA and IA. Similar to marine fish, C. gayi have an ACh-mediated vasoconstrictor pattern regulated by muscarinic receptors that activate a cyclooxygenase contraction pathway. These results suggest that the maintenance in vasoconstrictor mechanisms mediated by ACh→COX →vasoconstriction is conserved from fish to frogs.

Resumo Estudos feitos em peixes marinhos (I. conceptionis e G. laevifrons) têm demostrado que a indometacina bloqueia a contração arterial mediada por acetilcolina (ACh). O objetivo do presente estudo foi avaliar o efeito da via da ciclooxigenase na contração induzida por ACh em vasos arteriais da rã chilena Calyptocephalella gayi. Foram dissecadas regiões das artérias pulmonares (PA), dorsal (DA), mesentérica (MA) e ilíaca (IA) de seis espécimes adultos e realizados estudos de tensão isométrica utilizando curvas dose-resposta (CDR) de ACh (10-13 a 10-3 M) na presença de um antagonista muscarínico (atropina, 10-5 M) e um inibidor das ciclooxigenases (indometacina, 10-5 M). Todas as artérias evidenciaram uma resposta vasoconstritora mediada por ACh. Esta resposta vasoconstrictora foi suprimida na presença de atropina nas artérias DA, MA, IA e atenuada na PA. A indometacina suprimiu a vasoconstrição na artéria MA e atenuou a resposta nas artérias PA, DA e IA. Tal como os peixes marinhos, a C. gayi tem um padrão de vasoconstrição mediado por Ach que é regulado pelos receptores muscarínicos e pela ciclooxigenase. Estes resultados sugerem a conservação dos mecanismos vasoconstrictores mediados por ACh→COX em peixes e rãs.

Acetylcholine produces contractions mediated by the cyclooxygenase pathway in arterial vessels in the Chilean frog (Calyptocephalella gayi).

Previous studies performed in marine fish (I. conceptionis and G. laevifrons) showed that indomethacin blocked arterial contraction mediated by acetylcholine (ACh). The objective of this study was to determine if contraction induced by acetylcholine is mediated by the cyclooxygenase pathway in several arterial vessels in the Chilean frog Calyptocephalella gayi. Arteries from the pulmonary (PA), dorsal (DA), mesenteric (MA) and iliac (IA) regions were dissected from 6 adult specimens, and isometric tension studies were done using dose response curves (DRC) for ACh (10-13 to 10-3 M) in presence of a muscarinic antagonist (Atropine 10-5 M) and an unspecific inhibitor of cyclooxygenases (Indomethacin, 10-5M). All the studied arteries exhibited vasoconstriction mediated by ACh. This vasoconstriction was abolished in the presence of atropine in DA, MA and IA and attenuated in PA. Indomethacin abolished the vasoconstriction in MA and attenuated the response in PA, DA and IA. Similar to marine fish, C. gayi have an ACh-mediated vasoconstrictor pattern regulated by muscarinic receptors that activate a cyclooxygenase contraction pathway. These results suggest that the maintenance in vasoconstrictor mechanisms mediated by ACh→COX →vasoconstriction is conserved from fish to frogs.

Role of NO in arterial vascular function of intertidal fish (Girella laevifrons) and marine fish (Isacia conceptionis) / Papel do NO na função vascular arterial de peixes entremarés (Girella laevifrons) e peixes marinhos (Isacia conceptionis)

Abstract Previous studies performed in intertidal fish (Girella laevifrons),as well as marine fish (Isacia conceptionis), showed that acetylcholine (ACh) produced contractions mediated by cyclooxygenases that were dependent on the area and potency of contraction in several arterial vessels. Given that the role of nitric oxide is poorly understood in fish, the objective of our study was to evaluate the role of nitric oxide in branchial afferent (ABA), branchial efferent (ABE), dorsal (DA) and mesenteric (MA) arterial vessels from both Girella laevifrons and Isacia conceptionis. We studied afferent and efferent branchial, dorsal and mesenteric arteries that were dissected from 6 juvenile specimens. Isometric tension studies were done using dose response curves (DRC) for Ach (10–13 to 10–3 M) and blockade with L-NAME (10–5 M), and DRC for sodium nitroprusside (SNP, a donor of NO). L-NAME produced an attenuation of the contractile response in the dorsal, afferent and efferent branchial arteries and a potentiation of the contraction in the MA. SNP caused 70% dilation in the mesenteric artery and 40% in the dorsal artery. Our results suggest that Ach promotes precarious dilatation in MA mediated by NO; data that is supported by the use of sodium nitroprusside. In contrast, in the vessels DA, ABA and EBA our results support that the pathway Ach-NO-relaxation is absent in both species.

Resumo Estudos anteriores, realizados no peixe intertidal (Girellalaevifrons) no peixe marinho (Isacia conceptionis), mostram que a acetilcolina (Ach) provoca contrações mediadas por ciclooxigenases que eram dependentes da área e potencia da contração em vários vasos arteriais. Tendo em conta que o papel do óxido nítrico é mal compreendido em peixes, o objetivo do nosso estudo foi avaliar o papel do óxido nítrico em vasos arteriais de ambos os peixes Girella laevifrons e Isacia conceptionis. Nós estudamos os vasos aferente, branquial (ABA), eferente branquial (ABE), dorsal (DA) e mesentérica (MA), que foram dissecadas de seis espécimes juvenis. Estudos de tensão isométrica foram realizados utilizando as curvas de dose-resposta (DRC) para Ach (10–13 a 10–3M) e bloqueio com L-NAME (10–5 M), e na DRC para o nitroprussiato de sódio (SNP, doador do NO). L- NAME produziu uma atenuação da resposta contrátil nas artérias dorsais, aferentes e eferentes branquial e uma potenciação da contração no MA. SNP causaram 70% da dilatação da artéria mesentérica e 40% na artéria dorsal. Nossos resultados sugerem que Ach promove dilatação precária em MA mediada por NO; dados que é suportada pela utlilização de nitroprussiato de sódio. Em contraste, nos vasos de DA, ABA e EBA nossos resultados suportam que a via de Ach-NO-relaxamento está ausente em ambas as espécies.

Role of NO in arterial vascular function of intertidal fish (Girella laevifrons) and marine fish (Isacia conceptionis).

Previous studies performed in intertidal fish (Girella laevifrons),as well as marine fish (Isacia conceptionis), showed that acetylcholine (ACh) produced contractions mediated by cyclooxygenases that were dependent on the area and potency of contraction in several arterial vessels. Given that the role of nitric oxide is poorly understood in fish, the objective of our study was to evaluate the role of nitric oxide in branchial afferent (ABA), branchial efferent (ABE), dorsal (DA) and mesenteric (MA) arterial vessels from both Girella laevifrons and Isacia conceptionis. We studied afferent and efferent branchial, dorsal and mesenteric arteries that were dissected from 6 juvenile specimens. Isometric tension studies were done using dose response curves (DRC) for Ach (10-13 to 10-3 M) and blockade with L-NAME (10-5 M), and DRC for sodium nitroprusside (SNP, a donor of NO). L-NAME produced an attenuation of the contractile response in the dorsal, afferent and efferent branchial arteries and a potentiation of the contraction in the MA. SNP caused 70% dilation in the mesenteric artery and 40% in the dorsal artery. Our results suggest that Ach promotes precarious dilatation in MA mediated by NO; data that is supported by the use of sodium nitroprusside. In contrast, in the vessels DA, ABA and EBA our results support that the pathway Ach-NO-relaxation is absent in both species.

Acetylcholine produces contraction mediated by cyclooxigenase pathway in arterial vessels in the marine fish (Isacia conceptionis).

Preliminary studies showed that dorsal artery contraction mediated by acetylcholine (ACh) is blocked with indomethacin in intertidal fish (G. laevifrons). Our objective was to characterize the cholinergic pathway in several artery vessels of the I. conceptionis. Afferent and efferent branchial, dorsal and mesenteric arteries were dissected of 6 juvenile specimens, isometric tension studies were done using doses response curves (DRC) for Ach (10(-13) to 10(-3) M), and cholinergic pathways were obtained by blocking with atropine or indomethacin. CRC to ACh showed a pattern of high sensitivity only in efferente branchial artery and low sensibility in all vessels. Furthermore, these contractions were blocked in the presence of atropine and indomethacin in all vessels. Our results corroborate previous results observed in intertidal species that contraction induced by acetylcholine is mediated by receptors that activate a cyclooxygenase contraction pathway.

Vascular function in arteries of intertidal fish Girella laevifrons (Kyphosidae).

Preliminary studies showed that dorsal artery contraction mediated by acetylcholine (ACh) is blocked with indomethacin in intertidal fish (Girella laevifrons). Our objective was to characterise the cholinergic pathway in several artery vessels of the G. laevifrons. Afferent and efferent branchial, dorsal and mesenteric arteries were dissected of 6 juvenile specimens, isometric tension studies were done using dose response curves (DRC) for Ach (10(-13) to 10(-3) M), and cholinergic pathways were obtained by blocking with atropine or indomethacin. CRC to ACh showed a pattern of high and low sensitivity. Furthermore, these contractions were blocked in the presence of atropine and indomethacin in all vessels. Our results suggest that contraction observed with acetylcholine is mediated by receptors that activate a cyclooxygenase contraction pathway.

Fetal and postnatal pulmonary circulation in the Alto Andino.

Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the llama fetus compared to the sheep fetus. Altogether these data show that the fetal llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the llama. The llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.

Osteoporosis and multiple fractures in an antiretroviral-naive, HIV-positive child.

As a result of the increased incidence of osteopenia and osteoporosis in HIV-infected patients, numerous publications have suggested that there may be a link between bone metabolism alterations and HIV infection. The early bone loss seen in these patients was initially attributed to the use of highly active antiretroviral treatment (HAART) that included protease inhibitors. Recent studies, however, have suggested that it may be a direct consequence of the viral infection on bone metabolism, persistent activation of pro-inflammatory cytokines (TNFa), or altered vitamin D metabolism secondary to the virus, combined with subsequent factors (e.g., antiretroviral treatment) that aggravate the bone demineralization. We present an antiretroviral-naive 6-year-old girl with vertically transmitted HIV infection who presented with severe osteoporosis and multiple pathological fractures of the vertebrae, ribs, and upper and lower limbs. The child was treated with HAART, appropriate nutritional support for her age, physiotherapy and rehabilitation, calcium and vitamin D supplements, and alendronate therapy. After 6 weeks of treatment, the intense pain and muscle atrophy had disappeared and she was able to walk unassisted. At 6 months, bone mass had increased by 72%. The interest of this case lies in the presence of severe osteoporosis and multiple pathological fractures in an HIVinfected naive child. To date, this condition has only been described in patients treated with antiretrovirals. Moreover, this is the first reported HIV-positive pediatric patient treated with bisphosphonates, which proved to be highly successful.

Repeated doses of the perfluorocarbon FC-100 improve lung function of preterm lambs.

Intratracheal administration of a single dose of the perfluorocarbon FC-100 improves lung function in surfactant-deficient animals. In this study we compared the response to repeated doses of FC-100 (3 mL/kg 3% solution, n = 5) with that observed after administration of Exosurf (5 mL/kg, n = 5) to mechanically ventilated preterm lambs of 125 d of gestation. The initial dose of FC-100 rapidly increased arterial PO2, decreased arterial PCO2, and improved arterial pH. Also dynamic lung compliance markedly improved with this agent. Administration of an additional dose of FC-100 resulted in relatively similar changes, albeit of lesser magnitude than those observed with the initial dose. In contrast, Exosurf did not improve these variables even after three doses. All lambs treated with FC-100 survived the 6-h study period, whereas one of the five Exosurf-treated lambs survived (p < 0.05). Mean arterial blood pressure and heart rate decreased in those lambs that received FC-100, but not in surviving lambs that received Exosurf. Our data demonstrate that repeated intratracheal administration of the perfluorocarbon FC-100 improves lung function and survival of surfactant-deficient lambs better than the synthetic surfactant Exosurf. We speculate that tensio-active agents with properties different from surfactant, such as FC-100, might improve lung function in preterm neonates with diseases due to surfactant deficiency.

Anesthetic efficacy of eutectic prilocaine-lidocaine cream in pediatric oncology patients undergoing lumbar puncture.

OBJECTIVE: To evaluate the efficacy of eutectic mixture of local anesthetics 5% (Emla) in reducing pain associated with lumbar punctures in children. DESIGN: Prospective, double-blind, randomized, placebo-controlled trial. SETTING: University pediatric hospital. PATIENTS: Eleven pediatric oncology patients (mean age 6.6 y, range 4-16) who underwent 31 lumbar punctures. MAIN OUTCOME MEASURES: The analgesic effect was measured by using two methods. The first was a 10-point visual analog scale reported by the patient and the second was an 8-point behavioral pain scale assessed by the nurse who applied the cream. RESULTS: Emla cream was associated with significantly lower pain scores than those with placebo as measured by the patient when the puncture was successful on the first attempt (2.0 +/- 1.6 Emla group, 3.8 +/- 1.9 placebo group; p < 0.05). CONCLUSIONS: The use of Emla cream may reduce pain substantially only in patients who undergo a successful lumbar puncture on the first attempt.

Chemoreflex and endocrine components of cardiovascular responses to acute hypoxemia in the llama fetus.

We tested the hypothesis that the llama fetus has a blunted cardiovascular chemoreflex response to hypoxemia by investigating the effects of acute hypoxemia on perfusion pressure, heart rate, and the distribution of the combined ventricular output in 10 chronically instrumented fetal llamas at 0.6-0.7 gestation. Four llama fetuses had the carotid sinus nerves sectioned. In the intact fetuses, there was a marked bradycardia, an increase in perfusion pressure, and a pronounced peripheral vasoconstriction during hypoxemia. These cardiovascular responses during hypoxemia in intact fetuses were accompanied by a pronounced increase in plasma vasopressin, but not in plasma angiotensin II concentrations. Carotid denervation prevented the bradycardia at the onset of hypoxemia, but it did not affect the intense vasoconstriction during hypoxemia. Plasma vasopressin and angiotensin II levels were not measured in carotid-denervated fetuses. Our results do not support the hypothesis that the carotid chemoreflex during hypoxemia is blunted in the llama fetus. However, they emphasize that other mechanisms, such as increased vasopressin concentrations, operate to produce an intense vasoconstriction in hypoxemia. This intense vasoconstriction in the llama fetus during hypoxemia may reflect the influence of chronic exposure to the hypoxia of high altitude on the magnitude and gain of fetal cardiovascular responses to a superimposed acute episode of hypoxemia.

Cardiovascular responses to graded degrees of hypoxaemia in the llama fetus.

The fetal llama exposed to an intense degree of hypoxaemia did not increase cerebral blood flow, but showed a marked peripheral vasoconstriction. The same cardiovascular response is observed in fetal sheep submitted to a extremely severe hypoxaemia, when the initial compensatory vasodilatory mechanisms in brain and heart fail. To investigate whether the fetal llama responses to acute hypoxaemia are adaptive, or whether they are the result of a breakdown of mechanisms of blood flow redistribution that favours the central nervous system, we studied seven fetal llamas (0.6-0.7 of gestation) chronically-catheterized during 1 h of graded and progressive hypoxaemia. Fetal ascending aorta blood gases and fetal cardiac output and its distribution (radiolabelled-microspheres) were measured after 60 min of normoxaemia (B) and at the end of 20 min (H20), 40 min (H40) and 60 min (H60) of hypoxaemia. Data were analysed by ANOVA and Newman-Keuls tests. Each treatment resulted in a lower (P < 0.05) percentage of haemoglobin saturation than hypoxaemia; H40 was lower than H20, and H60 was lower than H20 and H40. No statistical difference was observed among treatments for cardiac output or cerebral blood flow. These results demonstrate that fetal cardiac output and brain blood flow are maintained at all degrees of hypoxaemia, indicating that these cardiovascular responses are an adaptive response in the llama fetus, rather than an index of cardiorespiratory decompensation.

Maternal administration of glucocorticoid and thyrotropin-releasing hormone enhances fetal lung maturation in undisturbed preterm lambs.

OBJECTIVE: We hypothesized that combined treatment with glucocorticoid plus thyrotropin-releasing hormone administered to pregnant ewes with preterm gestation accelerates fetal lung maturation of undisturbed lambs better than single hormonal treatment does. STUDY DESIGN: Twenty-five pregnant ewes at 123 days of gestation were randomized to receive (1) 0.9% sodium chloride (controls), (2) betamethasone (12 mg intramuscularly every 24 hours two times), (3) thyrotropin-releasing hormone (400 micrograms intravenously every 8 hours six times), or (4) thyrotropin-releasing hormone plus betamethasone. After delivery by cesarean section at 125 days fetal lamb lung compliance and alveolar lavage phospholipid content were determined. RESULTS: Betamethasone plus thyrotropin-releasing hormone significantly increased fetal lung compliance expressed as milliliters of air per gram of wet weight at 40 cm H2O and 5 cm H2O (0.82 +/- 0.13 and 0.35 +/- 0.10 ml/gm wet lung, respectively) versus betamethasone (0.37 +/- 0.02 and 0.07 +/- 0.02), thyrotropin-releasing hormone (0.38 +/- 0.02 and 0.14 +/- 0.03), and control (0.25 +/- 0.03 and 0.09 +/- 0.01) groups. Also, total phospholipids and saturated phosphatidylcholine concentrations in alveolar lavage were significantly higher in the combined betamethasone plus thyrotropin-releasing hormone group (27.3 +/- 4.9 and 16.9 +/- 4.3 micrograms/gm wet lung, respectively) versus betamethasone (10.9 +/- 3.5 and 6.7 +/- 2.1), thyrotropin-releasing hormone (15.2 +/- 5.6 and 7.3 +/- 2.0), and control (7.9 +/- 2.4 and 3.6 +/- 1.0) groups. CONCLUSION: Combined maternal administration of betamethasone plus thyrotropin-releasing hormone improves lung maturation in undisturbed fetal lambs at 125 days' gestation more than does either hormone given alone.

Primary meningococcal conjunctivitis: report of 21 patients and review.

Neisseria meningitidis is an uncommon cause of acute bacterial conjunctivitis. Twenty-one cases of primary meningococcal conjunctivitis (PMC) are reported herein and 63 cases published in the literature since 1899 are reviewed. In the 84 cases of PMC available for analysis, the male-to-female ratio was 1.76:1; nine of the patients were neonates, 55 were children, and 20 were adults. Conjunctivitis was unilateral in 66.3% of the patients. Gram stain of conjunctival exudate disclosed gram-negative diplococci in all cases in which it was done. Culture of the conjunctival exudate yielded N. meningitidis in all cases, and 44% of the isolated meningococci belonged to serogroup B. Ocular complications, which occurred in 15.5% of the patients, most frequently were corneal ulcers. Systemic meningococcal disease developed in 17.8% of the patients; the overall mortality was 13.3% for patients with PMC complicated by systemic disease. Development of systemic disease was significantly more frequent in patients receiving only topical therapy than in those treated with systemic therapy (31.71% vs. 2.38%; P = .001). Gram-negative diplococci observed in conjunctival exudate are an indication for systemic antibiotic therapy because of the risk of systemic complications associated with the use of topical therapy alone. When properly treated, patients with PMC have a favorable prognosis.

[Bile peritonitis caused by idiopathic perforation of a choledochal cyst]. / Cholépéritoine par perforation idiopathique d'un kyste du cholédoque.

The case of a 8 month-old infant presenting with biliary peritonitis, mild icterus and slowly progressive ascites is reported. Diagnosis was made through paracentesis showing higher bilirubin levels in the ascitic fluid (18 mg/100 ml) than in serum, and abdominal ultrasonography which showed pictures suggestive of choledochal cyst. A perforated choledochal cyst was surgically removed. The biliary duct was reconstructed by means of a hepatic Roux-en-Y jejunostomy. Postoperative course was satisfactory.

Boutonneuse fever.

Sixty children, aged between 2 and 10 years, had boutonneuse fever during the summer months of 1979 and 1980. They presented with fever and a generalised maculopapular rash. The tàche noire could be seen at the site of the tick bite in 38 (63%) of them. The antibody response, assayed nonspecifically, by the Weil-Felix reaction was positive in 52. A singe titre of more than 1:80 or a 4-fold increase between two paired specimens separated by a 7-day interval was considered diagnostic. Maximum titres were reached at the end of the second week of convalescence in 81% of patients. Treatment with oral oxytetracycline was effective in all cases.