Endoscopic resection of third ventricle colloid cysts using an ultrasonic aspirator.

An important step in the performance of endoscopic resection of colloid cysts of the third ventricle is the forced aspiration of cyst contents. The different consistencies these cysts may have can limit their complete resection and increase the likelihood of complications. The introduction of the ultrasonic neuroendoscopic aspirator allows cysts to be emptied more easily than with a conventional rigid aspirator, improving the feasibility of resection even in more solid cysts. The ability to regulate ultrasound and aspiration increases safety in a reduced and highly morbid space such as the third ventricle. Our objective was to determine the safety and efficiency of the ultrasonic aspirator for endoscopic resection of colloid cysts of the third ventricle. This was a retrospective descriptive study of patients with colloid cysts of the third ventricle undergoing neuroendoscopic resection using an ultrasonic aspirator between 2016-2023. Clinical, radiological, and procedural variables were studied. Mean, median and range were analyzed for quantitative variables and percentages and frequencies for qualitative variables. We present a series of 11 patients with colloid cysts of the third ventricle. The mean age was 44 years (27-69). All had biventricular hydrocephalus, with a mean cyst diameter of 15 mm (9-20). The lateral ventricle was accessed using the transforaminal approach in seven patients and the transchoroidal approach in three patients. All patients underwent septostomy. The mean endoscopy time was 40 min (29-68). Complete resection was possible in 10 patients. Median follow-up was 16 months (1-65) with 100% clinical improvement. At the end of follow-up, no patient had recurrence of the lesion. Based on our experience, the ultrasonic aspirator can be used safely and effectively for the resection of colloid cysts of the third ventricle, achieving high rates of complete resection with minimal postoperative complications.

External cranial expansion as treatment of intracranial hypertension. Technical note.

Intracranial hypertension may be idiopathic or due to multiple etiologies. Some bone dysplasias and chronic shunt overdrainage syndrome may sometimes lead to intracranial hypertension associated with craniocerebral disproportion due to thickening of cranial diploe. The internal cranial expansion procedure has been used for patients with intracranial hypertension, whether or not associated with craniocerebral disproportion. Its purpose is to increase the intracranial volume by drilling down the inner table. This technique enables the craniocerebral disproportion to be improved and intracranial hypertension reduced. In other etiologies of intracranial hypertension with non-thickened diploe, internal cranial expansion may not be enough to resolve the hypertension. For these cases we propose a modification of the technique by expanding the cranial vault outwards; external cranial expansion. We describe this technique as used in a pediatric patient who presented with chronic headache, tonsillar ectopia, and sleep apnea syndrome. This patient also had a multisuture craniosynostosis, a non-thickened diploe, and intracranial hypertension.

The role of women's leadership and gender equity in leadership and health system strengthening.

Gender equity is imperative to the attainment of healthy lives and wellbeing of all, and promoting gender equity in leadership in the health sector is an important part of this endeavour. This empirical research examines gender and leadership in the health sector, pooling learning from three complementary data sources: literature review, quantitative analysis of gender and leadership positions in global health organisations and qualitative life histories with health workers in Cambodia, Kenya and Zimbabwe. The findings highlight gender biases in leadership in global health, with women underrepresented. Gender roles, relations, norms and expectations shape progression and leadership at multiple levels. Increasing women's leadership within global health is an opportunity to further health system resilience and system responsiveness. We conclude with an agenda and tangible next steps of action for promoting women's leadership in health as a means to promote the global goals of achieving gender equity.

Analysis of risk factors for hydrocephalus development in newborn infants with germinal matrix hemorrhage.

AIM: The aim of this study was to analyze risk factors for the development of hydrocephalus in newborn infants with germinal matrix (GM) hemorrhage. METHODS: The study comprised 271 patients admitted to Carlos Haya University Hospital in Malaga with GM hemorrhage. The following data were recorded: gestational age, gender, twin birth, head circumference at birth, weight at birth, and Papile grade. Severe obstetrical (abruption, chorioamnionitis, pregnancy-induced hypertension, tocolytic treatment) and neonatal disorders (respiratory distress syndrome, neonatal infection, coagulation disorder, patent ductus arteriosus, necrotizing enterocolitis) were also recorded. Symptomatic hydrocephalus was diagnosed in the event of a progressive increase in head circumference and ventricular indices requiring shunting. RESULTS: Of the 271 patients, 139 (51%) developed posthemorrhagic ventriculomegaly; 47 patients (17%) developed symptomatic hydrocephalus and needed shunt implantation. We found a significant relationship between the development of symptomatic hydrocephalus and Papile grade, lower gestational age, lower birth weight, twin birth, and neonatal infection. CONCLUSION: Awareness of risk factors for the development of hydrocephalus in newborn infants with GM hemorrhage should be emphasized in order to enable an early diagnosis of ventriculomegaly and symptomatic hydrocephalus and thus make a correct therapeutic decision.

Endoscopic transchoroidal and transforaminal approaches for resection of third ventricular colloid cysts.

To review our experience over 10 years in endoscopic resection of third ventricular colloid cysts, describing the details of the transventricular-transchoroidal approach used in selected patients. This series included 24 patients with colloid cysts of the third ventricle treated in our department between October 2001 and January 2013 using an endoscopic approach. Clinical presentation, preoperative radiological findings, endoscopic technique employed, and complications were assessed in all patients. The mean length of patient follow-up was 5.16 years. The most common symptom was headache (75%). The average size of the resected colloid cysts was 16.25 mm, the maximum diameter measured in cranial magnetic resonance imaging. Resection was transforaminal in 16 cases (66.7%), transchoroidal in 7 (29.17%), and transseptal in 1; macroscopically complete resection was achieved in 23 of 24 procedures (95.8%). Complications included three intraventricular hemorrhages, four memory deficits (two of them transient), one case of temporary potomania, two soft tissue infections, and one meningitis. There were no statistically significant differences between the route of resection and number of complications. The Glasgow Outcome Scale at 1 year after surgery was 5 in 82.6% of the patients. A transventricular endoscopic approach allows macroscopically complete resection of third ventricle colloid cysts in most cases. The option of opening the choroidal fissure (transventricular-transchoroidal approach) during the procedure can address third ventricle colloid cysts that do not emerge sufficiently through the foramen of Monro without increasing procedure-related morbidity.

Endoscopic third ventriculostomy: can we predict success during surgery?

Endoscopic third ventriculostomy (ETV) is widely used as an alternative technique for hydrocephalus treatment. ETV success or failure may be influenced by numerous factors. In this study, we have analyzed preoperative and intraoperative risk factors and suggest an intraoperative scale to predict etV failure. Fifty-one patients (27 adults and 24 children) underwent an etV at Carlos Haya University Hospital, Malaga. Intraoperative video records were assessed and the following intraoperative findings were recorded: (1) abnormal ventricular anatomy, (2) intraoperative incident, (3) Liliequist membrane opening in a second endoscopic maneuver, (4) thickened or scarred membranes in the subarachnoid space, (5) absence or "weakness" of pulsation of third ventricle floor at etV completion, and (6) floppy premammillary membrane that needs edge coagulation. An intraoperative scale ranging from 0 to 6 points was performed. A significant relation was found between a higher result on the prognosis scale and etV failure (p < 0.0001). An absence or weakness of pulsation of the third ventricle floor at etV completion was significantly related to etV failure (p < 0.0001). The presence of thickened or scarred membranes in the subarachnoid space was significantly related to etV failure (p < 0.04) as well as the Liliequist membrane opening in a second endoscopic maneuver (p < 0.008). Intraoperative factors should be taken into account for prediction of etV success. More studies with larger case series are needed to determine the influence of all intraoperative factors over etV success.

Ventriculoperitoneal shunt as a primary neurosurgical procedure in newborn posthemorrhagic hydrocephalus: report of a series of 47 shunted patients.

PURPOSE: Intraventricular hemorrhage is the most common cause of infantile acquired hydrocephalus. Our objective is to determine if the implantation of ventriculoperitoneal shunt in posthemorrhagic hydrocephalus as a primary and definitive neurosurgical treatment, with no previous temporary procedures, would decrease complication rates with good functional outcomes. METHODS: Two hundred seventy-one patients with germinal matrix hemorrhage were diagnosed at the Carlos Haya Hospital between 2003 and 2010. Forty-seven patients underwent ventriculoperitoneal shunt after developing symptomatic hydrocephalus. The minimum weight required for shunt implantation was 1,500 g. We recorded complications related to the surgical procedure and analyzed functional state with a self-developed four-grade scale. RESULTS: One hundred thirty-nine (51.3 %) patients with intraventricular hemorrhage developed ventricular dilatation, but only 47 patients (17.34 %) needed shunting. In seven cases, temporary neurosurgical procedures were performed, but in all of them, this was followed by ventriculoperitoneal shunt implantation. The infection rate was 4.25 %, and shunt obstruction rate was 4.25 %. More than 80 % of patients were classified as good or excellent functional state. Mean follow-up period was 38.75 months (SD, 27.09; range, 1-102 months). CONCLUSIONS: Ventriculoperitoneal shunting as a primary neurosurgical treatment in posthemorrhagic hydrocephalus would decrease surgical morbidity with good functional outcome.

Efectividad de una intervención para la mejora del cumplimiento en la higiene de manos en un hospital de tercer nivel / Effectiveness of an intervention to improve the compliance of hand hygiene in a tertiary hospital

Objetivo. El objetivo es evaluar la efectividad de una intervención orientada a la higiene de manos (HM) así como la identificación de los factores relacionados con el no cumplimiento. Material y métodos. Estudio de intervención antes-después con dos cortes transversales de observación directa de cumplimiento de HM. La intervención se dirigió a todos los profesionales sanitarios y servicios hospitalarios que tienen contacto directo con los pacientes o el medio ambiente que los rodea. Se realizaron 160 periodos de observación en cada corte, registrándose 5.245 oportunidades de HM (OHM) en 947 profesionales. Resultados. Se observa un incremento significativo del 7,7% (intervalo de confianza (IC) 95%: 5,5-9,9; p<0,001) en el grado de cumplimiento de HM (pre-intervención: 17,4% [IC 95%: 16,0-18,9]; post-intervención: 25,2% [IC 95%: 23,5-26,9]). El turno de mañana (odds ratio (OR): 0,32; IC 95%: 0,24-0,42), la categoría de enfermería (OR: 0,44; IC 95%: 0,29-0,65), el área de cuidados intensivos (OR: 0,14; IC 95%: 0,10-0,18), el no uso de guantes (OR: 0,58; IC 95%: 0,48-0,69), las OHM realizadas después de contactos de alto riesgo (OR: 0,30: IC 95%: 0,22-0,41) y después de contactos de bajo riesgo (OR: 0,43; IC 95%: 0,32-0,58) se relacionaron de manera independiente con el no cumplimiento. Conclusiones. La campaña realizada mostró un efecto independiente significativo en la mejora de la HM. Es necesario el diseño en los centros sanitarios de estrategias multimodales para incrementar la HM en los profesionales(AU)

Objective. The aim of the study is to assess the effectiveness of an intervention to improve the compliance with hand hygiene (HH) and the detection of factors associated with non-compliance. Methods. A before and after intervention study with two cross-sectional and direct observations of HH compliance was performed. The intervention was targeted at all the health workers and hospital departments directly related with patients and their healthcare environment. One hundred and sixty observation periods were included in each cross-sectional observation, accounting for a total of 5,245 observed opportunities of HH among 947 health workers. Results. Hand hygiene compliance showed a significant increase of 7.7% (95% CI: 5.5-9.9; P<.001) with a pre-intervention and post-intervention HH compliance of 17.4% (95% CI: 16.0-18.9) and 25.5% (95% CI: 23.5-26.9), respectively. The following variables showed an independent association with the non-compliance of HH: morning shift (0.32; 95% CI: 0.24-0.42), being a nurse (OR: 0.44; 95%CI: 0.29-0.65), working in an intensive care unit (OR: 0.14: 95%CI: 0.10-0.18), non-use of gloves (OR:0.58: 95% CI:0.48-0.69), observed opportunities of HH arising after high risk contact (OR:0.30: 95% CI: 0.22-0.41) and after low risk contact (OR:0.43: 95% CI:0.32-0.58). Conclusions. The intervention has independently and significantly improved hand hygiene in the hospital. Multimodal strategies need to be designed in healthcare settings in order to increase HH compliance among health workers(AU)

[Effectiveness of an intervention to improve the compliance of hand hygiene in a tertiary hospital]. / Efectividad de una intervención para la mejora del cumplimiento en la higiene de manos en un hospital de tercer nivel.

OBJECTIVE: The aim of the study is to assess the effectiveness of an intervention to improve the compliance with hand hygiene (HH) and the detection of factors associated with non-compliance. METHODS: A before and after intervention study with two cross-sectional and direct observations of HH compliance was performed. The intervention was targeted at all the health workers and hospital departments directly related with patients and their healthcare environment. One hundred and sixty observation periods were included in each cross-sectional observation, accounting for a total of 5,245 observed opportunities of HH among 947 health workers. RESULTS: Hand hygiene compliance showed a significant increase of 7.7% (95% CI: 5.5-9.9; P<.001) with a pre-intervention and post-intervention HH compliance of 17.4% (95% CI: 16.0-18.9) and 25.5% (95% CI: 23.5-26.9), respectively. The following variables showed an independent association with the non-compliance of HH: morning shift (0.32; 95% CI: 0.24-0.42), being a nurse (OR: 0.44; 95%CI: 0.29-0.65), working in an intensive care unit (OR: 0.14: 95%CI: 0.10-0.18), non-use of gloves (OR:0.58: 95% CI:0.48-0.69), observed opportunities of HH arising after high risk contact (OR:0.30: 95% CI: 0.22-0.41) and after low risk contact (OR:0.43: 95% CI:0.32-0.58). CONCLUSIONS: The intervention has independently and significantly improved hand hygiene in the hospital. Multimodal strategies need to be designed in healthcare settings in order to increase HH compliance among health workers.

[Posthemorrhagic hydrocephalus in the preterm infant: current evidence in diagnosis and treatment]. / Hidrocefalia poshemorrágica asociada a la prematuridad: evidencia disponible diagnóstica y terapéutica.

Intraventricular haemorrhage and posthemorrhagic hydrocephalus are the most important neurological complications in preterm infants during the neonatal period. The prevalence of germinal matrix intraventricular haemorrhage widely varies depending on the population of study, but it is in any case increasing due both to the higher incidence of multiple and preterm deliveries as well as the longer survival of preterm infants favoured by recent advances in perinatal care. It is therefore of the utmost convenience to be familiar with the most important clinical evidence regarding this entity. However, the available evidence is often incomplete and piecemeal. The objective of the present review is to summarise the main diagnostic and therapeutic points regarding preterm related posthemorrhagic hydrocephalus. The participants of the working-group in Pediatric Neurosurgery of the Spanish Society of Neurosurgery were asked to write these recommendations down. This hopefully represents the first step towards the definition of a clinical guide in the treatment of complications related to periventricular hemorrhage of the preterm infants.

Hidrocefalia poshemorrágica asociada a la prematuridad: evidencia disponible diagnóstica y terapéutica / Posthemorrhagic hydrocephalus in the preterm infant: current evidence in diagnosis and treatment

La hemorragia de la matriz germinal y la hidrocefalia poshemorrágica son las complicaciones neuroquirúrgicas más frecuentes en los pacientes recién nacidos pretérmino91. La incidencia de estas complicaciones es muy variable según las series consultadas19,36,47,56,61,71,93, pero su prevalencia está en cualquier caso en aumento debido tanto a la mayor incidencia de embarazos múltiples y partos prematuros en relación al avance de las nuevas técnicas de fertilización, como a la mayor supervivencia de estos pacientes merced a los recientes avances en los cuidados perinatales85. En este contexto resulta esencial disponer de un conocimiento preciso y concreto de las recomendaciones diagnósticas y terapéuticas en referencia a esta entidad. Sin embargo, la evidencia disponible al respecto es a menudo fragmentada e incompleta. El objetivo de la presente revisión es proporcionar un resumen actualizado de los principales aspectos diagnósticos y terapéuticos de la hidrocefalia poshemorrágica asociada a la prematuridad. Para ello se ha solicitado a los miembros del grupo de trabajo de Neurocirugía Pediátrica de la Sociedad Española de Neurocirugía que revisen las cuestiones más relevantes en referencia a esta patología. Esto supone el primer paso para la elaboración de una guía clínica común para el tratamiento de las complicaciones asociadas a la hemorragia intra y periventricular del prematuro (AU)

Intraventricular haemorrhage and posthemorrhagic hydrocephalus are the most important neurological complications in preterm infants during the neonatal period91. The prevalence of germinal matrixintraventricular haemorrhage widely varies depending on the population of study19,36,47,56,61,71,93, but it is in any case increasing due both to the higher incidence of multiple and preterm deliveries as well as the longer survival of preterm infants favoured by recent advances in perinatal care85. It is therefore of the utmost convenience to be familiar with the most important clinical evidence regarding this entity. However, the available evidence is often incomplete and piecemeal. The objective of the present review is to summarise the main diagnostic and therapeutic points regarding preterm-related posthemorrhagic hydrocephalus. The participants of the working-group in Pediatric Neurosurgery of the Spanish Society of Neurosurgery were asked to write these recommendations down. This hopefully represents the first step towards the definition of a clinical guide in the treatment of complications related to periventricular hemorrhage of the preterm infants (AU)

Entrecruzamiento de cordones en la gestación gemelar monocorial monoamniótica / Cord entanglement in monochorionic monoamniotic twin pregnancies

La gestación gemelar monocorial monoamniótica presenta alto riesgo de muerte fetal en relación a complicaciones generales de las gestaciones gemelares así como específicas de la monoamniocidad, siendo la más grave la muerte fetal por entrecruzamiento de cordones, el cual se presenta en prácticamente la totalidad de los casos. En el manejo de la gestación monocorial monoamniótica es fundamental un correcto diagnóstico precoz ecográfico, así como un manejo y vigilancia estricta para detectar signos de entrecruzamiento de cordones que permitan evitar la progresión a muerte fetal intraútero. La necesidad de hospitalización y el momento de finalización de la gestación siguen generando controversia en la literatura médica (AU)

Monochorial monoamniotic twins are at high risk of fetal death due to the general complications seen in multiple gestations, as well as those specific to this type of pregnancy. The most severe complication in these pregnancies is fetal death due to cord entanglement, which occurs in almost all cases. Early ultrasonographic diagnosis and intensive prenatal surveillance are essential for the early detection of cord entanglement and the prevention of fetal death. The need for in-hospital management and the exact gestational age for delivery continue to generate controversy in the literature (AU)

Extraction of mitochondrial DNA from tooth dentin: application of two techniques

Mitochondrial DNA (mtDNA) is a hereditary material located in mitochondria and is normally maternally inherited. Mutational analysis performed on mtDNA proved that the mutations are closely related with a number of genetic illnesses, besides being exploitable for forensic identification. Those findings imply the importance of mtDNA in the scientific field. MtDNA can be found in abundance in tooth dentin where it is kept protected by the enamel, the hardest outer part of the tooth. In this study, two techniques of mtDNA extraction were compared to determine the efficacy between the two techniques. Teeth used for the study was collected from Dental Clinic, Hospital Universiti Sains Malaysia. After the removal of tooth from the tooth socket of the patient, the tooth was kept at -20C until use. Later, pulp tissue and enamel was excised using dental bur and only the root dentin was utilized for the isolation of mtDNA by crushing it mechanically into powdered form. MtDNA was extracted using the two published methods, Pfeifer and Budowle and then subjected to spectrophotometry DNA quantification and purity, Polymerase chain reaction (PCR) amplification of hypervariable-two region of mtDNA, followed by DNA sequencing to analyze the reliability of the extraction techniques. In conclusion, both techniques proved to be efficient and capable for the extraction of mtDNA from tooth dentin.

Comparative analysis of Phytophthora infestans induced gene expression in potato cultivars with different levels of resistance.

Differential gene expression was analyzed after infection with Phytophthora infestans in six potato cultivars with different levels of resistance to late blight. To verify the infection of the potato leaflets, the amount of phytopathogen mRNA within the plant material was quantified by real-time quantitative PCR. The expression of 182 genes selected from two subtracted cDNA libraries was studied with cDNA array hybridization using RNA from non-infected and infected potato leaflets. Gene up- and down-regulation were clearly detectable in all cultivars 72 h post inoculation. Gene expression patterns in susceptible cultivars differed from those in potato varieties with a higher level of resistance. In general, a stronger gene induction was observed in the susceptible cultivars compared to the moderately to highly resistant potato varieties. Five genes with the highest homology to stress and/or defence-related genes were induced specifically in the susceptible cultivars. Four genes responded to pathogen attack independently of the level of resistance of the cultivar used, and three genes were repressed in infected tissue of most cultivars. Even in the absence of P. infestans infection, six genes showed higher expression levels in the somewhat resistant cultivars Bettina and Matilda. Possible reasons for the different levels of gene expression are discussed.

[Central neurocytoma: analysis of three cases and review of the literature]. / Neurocitoma central: a propósito de tres casos y revisión de la literatura.

INTRODUCTION AND CLINICAL CASES: Three cases of central neurocytoma, confirmed by immunohistochemical study are reported. The central neurocytoma has recently been added to the differential diagnosis of intraventricular tumors. It is more frequent than previously thought, with high incidence in young patients. The positivity for synaptophysin and neuron specific enolase, the negativity for neurofilament protein and glial fibrillary acid protein, and the finding of elements of neuronal differentiation on electron microscopy, are the main pathological features of these tumors. CONCLUSION: The surgical treatment is the election, and radiotherapy is reserved for malignant cases or recurrence.

[Spontaneous epidural spinal hematoma: report of 2 cases and review of the literature]. / Hematoma epidural espinal espontáneo: presentación de 2 casos y revisión de la bibliografía.

Spontaneous spinal epidural hematoma is an uncommon cause of cord compression. This lesion has been correlated with some precipitant factors, but frequently is idiopathic. It's a unusual process, more uncommon in children, and there are only 350 cases reported in the literature. Etiology is unknown and there are several theories about it. The clinical presentation is remarkably uniform, with local back and radicular pain followed by sensory and motor disfunction. Early diagnosis and treatment are very important for the functional recovery of the patient. In this article, the literature is reviewed, especially the etiological and therapeutic aspects, and two new cases are reported. These cases can help to define the etiology of this entity.

The effect of selective phosphodiesterase 3 and 4 isoenzyme inhibitors and established anti-asthma drugs on inflammatory cell activation.

1. This study aimed to evaluate the effects of phosphodiesterase (PDE) inhibitors and currently prescribed anti-asthma drugs for their ability to inhibit inflammatory cell activation in vitro. 2. Alveolar macrophages and eosinophils were isolated from the bronchoalveolar lavage (BAL) fluid of ovalbumin (Ovalb)-sensitized guinea-pigs. Opsonized zymosan (OZ) and PAF stimulated leukotriene B4 (LTB4) release from eosinophils was measured by radioimmunoassay. Ovalb-induced superoxide generation was measured by reduction of cytochrome C. 3. Monocytes were separated from human peripheral venous blood and mast cells were dispersed from human lung fragments. Lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-alpha) release from monocytes was measured by ELISA and anti-IgE stimulated histamine release from mast cells was measured by a radioenzymatic method. 4. The beta 2 agonist, salbutamol inhibited TNF-alpha release from monocytes and histamine release from mast cells whilst having no effect on eosinophil-derived LTB4 release or macrophage superoxide generation. 5. The PDE 3 inhibitor, milrinone produced a concentration-related inhibition of TNF-alpha release from monocytes which achieved statistical significance at 10(-5) M but inhibited LTB4 release from eosinophils and superoxide generation from macrophages only at the highest concentration (10(-3) M) examined. Milrinone had no effect on histamine release from mast cells. 6. The selective PDE 4 inhibitors, denbufylline and rolipram and the corticosteroid, beclomethasone produced a concentration-related inhibition of LTB4 release from eosinophils, TNF-alpha release from monocytes and superoxide generation from alveolar macrophages whilst having no effect on histamine release from mast cells. 7. The mixed PDE 3/4 inhibitor, benzafentrine produced a concentration-related inhibition of LTB4 release from eosinophils, TNF-alpha release from monocytes, superoxide generation from alveolar macrophages and histamine release from mast cells. 8. In conclusion these data clearly show that both established anti-asthma medication as well as PDE inhibitors have the potential to inhibit inflammatory cell activation in vitro but that the anti-secretory actions of beta 2 agonists, corticosteroids and PDE inhibitors are distinct.

Characterization of big endothelin-1-induced contraction in rabbit saphenous artery.

We have characterized the endothelin-converting enzyme (ECE)-like activity involved in big endothelin (ET)-1-induced contraction in rabbit saphenous artery (RSA). Big ET-1 30 nM caused a contraction that was independent of the vascular endothelium. Phosphoramidon and the neutral endopeptidase (NEP) inhibitors thiorphan and candoxatrilat blocked the vasoconstriction caused by big ET-1 in endothelium-denuded RSA. Candoxatrilat (IC50 17 nM) and thiorphan (IC50 2.5 nM), were 5- to 30-fold more potent than phosphoramidon (IC50 83 nM). Other protease inhibitors were inactive. In cultured endothelial cells the ET-1 release was inhibited only by phosphoramidon (IC50 16 microM) but at a concentration 200-fold that required an endothelium-denuded RSA. In conclusion, we can speculate that the big ET-1 contraction in RSA is mediated by an ECE, probably present on smooth muscle cells, which is susceptible to NEP inhibitors and is different from the ECE on endothelial cells.