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Con el objetivo de asociar el tamaño de los ornamentos sexuales con caracteres reproductivos y productivos en gallinas del cruzamiento de tres vías Campero Casilda se calcularon, en 97 aves de 30 semanas, los índices de cresta [IC: longitud x alto] y barbilla [IB: longitud x ancho]. Los datos individuales se graficaron en un sistema de ejes cartesianos (X: IC; Y: IB) el que se dividió en cuatro cuadrantes mediante dos rectas que intersectan a cada eje a nivel de los valores medios. Se identificaron las aves con valores extremos de ambos índices [Cuadrante I (CI): > IC > IB y Cuadrante III (CIII): < IC < IB] y, para cada una de ellas, se registraron los caracteres productivos a la madurez sexual, cuatro indicadores de desarrollo óseo a las 30 y 71 semanas, los patrones dinámicos del peso corporal y el peso del huevo y la relación de conversión en huevos en la primera parte del ciclo de postura. Las aves con mayor desarrollo de los ornamentos sexuales (a) fueron más precoces y comenzaron la postura con huevos de menor peso, pero con similar regularidad y uniformidad, presentando (b) mayor longitud del tarso y del fémur en ambas edades, mayor diámetro del tarso a las 30 semanas y mayor longitud de la tibia a las 71 semanas de edad (c) mayor tasa de crecimiento exponencial entre la sexta y la vigésima semana pero similar patrón de crecimiento global, (d) menor peso asintótico del huevo, menor tasa de maduración para el carácter y menor peso teórico del primer huevo y (e) mayor número de huevos de menor peso y similar relación de conversión entre las 26 y 35 semanas. La combinación del tamaño de los ornamentos sexuales se presenta como una alternativa para la selección temprana de los reproductores.

RESUMEN. El pollo Campero INTA es un tipo de ave destinado a la producción de carne en sistemas semi-intensivos. En Argentina es distribuido por el Programa Pro-Huerta para la autoproducción de alimentos y venta de excedentes por parte de sectores de la población en situación de vulnerabilidad alimentaria. Asimismo, representa una potencial alternativa productiva para un mercado vinculado con la demanda de productos naturales y el respeto por el bienestar animal. En el caso del Programa Prohuerta, los pollos camperos son distribuidos a zonas con muy diferente impacto de las variables medioambientales particularmente climáticas, situación en la que las interacciones genotipo x ambiente cobran particular trascendencia. El objetivo de este trabajo fue evaluar el efecto de la estación de crianza sobre las variables productivas habitualmente analizadas como salidas en estos sistemas de producción en pollos campero macho, derivados de dos modelos genéticos de cruzamientos terminales: el híbrido experimental de tres vías Campero Casilda y el híbrido simple Campero INTA. La evidencia obtenida indica que Campero Casilda presenta mayor estabilidad ante el cambio de estación en términos de eficiencia de uso del alimento. Las aves criadas en primavera presentan mayor proporción de cortes valiosos y bajo contenido de grasa respuestas asociadas a un menor peso corporal atribuible a los efectos detrimentales de la temperatura ambiente sobre la tasa de crecimiento. ABSTRACT. Campero chicken INTA is a meat type of chicken raised in semi-intensive systems. In Argentina it is distributed by the Pro-Huerta Program for the self-production of food and the sale of surpluses by sectors of the population in a situation of food vulnerability. It also represents a potential productive alternative for a market linked to the demand for natural products and respect for animal welfare. In the case of the Pro-Huerta Program, Campero chickens are distributed to areas with a very different impact of environmental variables, particularly climatic, in which the genotype x environment interactions take on particular importance. The aim of this work was to evaluate the effect of the climatic season on the productive variables routinely analyzed as outputs in these production systems, in male Campero chickens derived from two genetic models of terminal crosses: the three-way experimental cross Campero Casilda and the single-cross Campero INTA. The evidence indicates that Campero Casilda presents greater stability than Campero INTA in the face of the change of season in terms of efficiency of food use. Birds reared in spring have a higher proportion of valuable cuts and a lower fat content than those reared in autumn, a response associated with their lower body weight attributable to the detrimental effects of temperature on growth rate.

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Le syndrome hémophagocytaire (SH) se présente classiquement sous la forme de cytopénies fébriles accompagnées d’un syndrome tumoral, le plus souvent dans le cadre d’un déficit immunitaire sous-jacent. Les formes les plus sévères s’accompagnent de défaillances d’organes qui peuvent conduire le patient en réanimation. Les principales étiologies de SH sont les infections, les hémopathies et les maladies de système. Les infections associées au SH sont majoritairement virales, liées à l’EBV, au CMV et aux autres virus du groupe herpes. Les infections bactériennes sont dominées par les mycobactéries, et les parasites sont essentiellement représentés par la leishmaniose et la toxoplasmose. Enfin, parmi les infections fongiques, l’histoplasmose est à rechercher en priorité. La prise en charge thérapeutique du SH associé aux infections comprend trois volets : le traitement de l’infection, les traitements de support et le traitement du SH. Les principaux traitements proposés dans le cadre du SH associé aux infections sont les corticoïdes, les immunoglobulines polyvalentes et l’étoposide. À la phase initiale, c’est principalement la gravité des patients (défaillances d’organes) qui guidera la décision d’administrer ou non un traitement spécifique du SH. Un aspect important de la prise en charge thérapeutique est la recherche systématique d’un déficit immunitaire sous-jacent, qui pourra faire l’objet d’une prise en charge spécifique. Le bilan minimal comprendra la recherche d’une infection par le VIH, la recherche d’une hémopathie lymphoïde sous-jacente (maladie de Hodgkin, lymphome non hodgkinien, maladie de Castleman) et la recherche d’arguments en faveur d’une maladie systémique (Lupus et maladie de Still).

Introduction La pneumopathie a Pneumocystis jirovecii (PcP) est associee a un recours frequent aux soins intensifs (USI), a la ventilation mecanique et a un pronostic pejoratif. L’initiation precoce d’une corticotherapie adjuvante dans les formes severes de PcP permet une reduction significative de la mortalite chez les patients infectes par le virus de l’immunodeficience humaine (VIH), mais son benefice reste controverse chez les patients non infectes par le VIH (NVIH). Chez les patients hospitalises en USI, l’immunodepression et le recours a la corticotherapie au cours d’infection respiratoire severe comme la grippe est associee au risque de co-infections respiratoires ainsi qu’a la mortalite. L’objectif de cette etude etait d’evaluer l’epidemiologie et l’impact pronostique des co-infections respiratoires lors du diagnostic de PcP. Materiels et methodes Nous avons conduit une etude observationnelle retrospective, bicentrique, entre janvier 2011 et avril 2019, incluant tous les patients pour lesquels le diagnostic de PcP a ete etabli apres confirmation mycologique (examen direct positif et/ou qPCR positive) sur des prelevements respiratoires profonds (liquide d’aspiration tracheo-bronchique, lavage broncho-alveolaire (LBA)). La co-infection respiratoire etait definie par la detection d’un autre micro-organisme pathogene sur le meme prelevement que celui ayant conduit au diagnostic de PcP. Les analyses ont ete realisees sur la population globale puis sur les sous-groupes VIH et NVIH. Resultats A partir des 7 882 prelevements respiratoires analyses durant la periode de l’etude, 328 patients ont ete inclus. La moyenne d’âge etait de 56,7 ± 14,9 ans, 193 (58,8 %) etaient des hommes, 74 (22,6 %) etaient infectes par le VIH, le score SOFA moyen a l’admission etait de 3,5 ± 3,3, 168 (51,2 %) patients ont recu une corticotherapie adjuvante et la mortalite a J-90 etait de 25,3 %. Une co-infection respiratoire a ete mise en evidence chez 180 patients (54,9 %): 125 (38,1 %) co-infections virales dont 79 (24,1 %) a cytomegalovirus (CMV), 76 (23,2 %) co-infections bacteriennes et 36 (11 %) co-infections parasitaires ou fongiques. En analyse multivariee, la presence d’une co-infection respiratoire par le CMV (OR 3,44; 1,24-2,90; p = 0,02), de tumeur solide en cours de prise en charge (OR 11,8; 1,90-78; p = 0,008) et un score SOFA eleve a l’admission (OR 1,62; 1,34-2,05; p Conclusion La co-infection respiratoire par le CMV au diagnostic de PcP est independamment associee au risque de mortalite a J-90, en particulier chez les patients NVIH avec une corticotherapie adjuvante. Ces resultats suggerent que la recherche de co-infection respiratoire a CMV devrait etre systematiquement realisee au diagnostic de PcP dans le LBA, notamment avant d’envisager une corticotherapie adjuvante chez les patients NVIH. Des etudes interventionnelles prospectives prenant en compte la presence du CMV au diagnostic de PcP afin d’evaluer l’interet de la corticotherapie adjuvante et/ou du traitement anti-CMV sur le pronostic des patients NVIH semblent donc justifiees.

Introduction Le purpura thrombotique thrombocytopenique acquis (PTTa) est une maladie rare, engageant le pronostic vital, et qui necessite l’initiation urgente de plasmaphereses. Le diagnostic de certitude repose sur la mise en evidence d’une activite ADAMTS13 effondree, resultat qui n’est obtenu qu’en plusieurs jours. L’initiation des plasmaphereses ne reposent donc que sur des elements cliniques et biologiques simples. L’objectif de cette etude etait d’analyser : – les elements contribuant au retard diagnostic dans le PTTa, – l’impact pronostic de ce retard sur l’evolution initiale du PTTa. Patients et methodes Il s’agit d’une etude monocentrique retrospective incluant des patients pris en charge au CHU de Nantes entre 2005 et 2020 pour un premier episode aigu de PTTa, defini par une micro-angiopathie thrombotique associee a un dosage de l’ADAMTS13 24 h) et diagnostic immediat ( Resultats Parmi les 41 patients evalues, 38 ont ete inclus, dont 18 (47 %) ont eu un diagnostic tardif (delai median : 5,5 jours). La premiere evaluation hospitaliere avait lieu dans un service d’urgence dans 70 % des cas. Dans le groupe diagnostic retarde, on observait davantage de comorbidites potentiellement responsables de thrombopenie (connectivite, hepatite C, immunosuppresseur) ou de facteur declenchant le PTTa (chirurgie, grossesse). Le principal diagnostic errone initial etait le purpura thrombopenique immunologique (PTI) [13 (72 %), dont 6 syndromes d’Evans]. Il n’y avait pas de difference significative en termes de signes cliniques initiaux entre les deux groupes. Chez les patients diagnostiques avec retard, l’anemie etait moins frequente [12 (67 %) vs 19 (95 %), p = 0,04] et les schizocytes plus souvent Conclusion Lors de leur premiere evaluation hospitaliere, pres de la moitie des patients atteints de PTTa sont mal diagnostiques, et le plus souvent etiquetes PTI. Ceci a un impact negatif sur le pronostic. Les praticiens de premiere ligne jouent un role essentiel pour le diagnostic precoce de PTTa, qui doit etre evoque chez tout patient presentant une thrombopenie marquee, y compris lorsqu’un diagnostic alternatif moins rare parait possible. En l’absence de dosage rapide d’ADAMTS13, il faut souligner la valeur des “petits” signes d’organes (cephalees, douleurs abdominales…) et du bilan d’hemolyse systematique, et, a contrario, les limites de la recherche de schizocytes, qui doit etre repetee en cas de “negativite”.

L’amelioration de la survie des patients d’oncohematologie et des patients immunodeprimes (transplantes d’organes, maladies auto-immunes) et l’augmentation de l’arsenal therapeutique au cours des 20 dernieres annees ont fait apparaitre de nouveaux profils de toxicite des traitements utilises. Si les infections severes restent la principale cause d’admission en reanimation chez ces patients, des complications cardiovasculaires variees peuvent survenir au cours des multiples lignes de traitement administrees. La toxicite cardiaque des anthracyclines est decrite depuis 1950 et est tres bien documentee. Plus recemment, de multiples effets cardiovasculaires des therapies ciblees (anticorps monoclonaux et inhibiteurs de tyrosine-kinase [ITK]) ont ete rapportes, parmi lesquels: l’hypertension arterielle, l’insuffisance cardiaque, l’ischemie myocardique, les troubles du rythme ou de la conduction cardiaques et l’epanchement pericardique. Un risque accru d’evenements thromboemboliques veineux, mais aussi arteriels, existe avec la majorite des chimiotherapies, hormonotherapies et therapies ciblees, pouvant conduire le patient en reanimation dans les formes graves ou en raison de complications hemorragiques survenant sous traitement anticoagulant. Des atteintes microvasculaires attribuables aux traitements anticancereux et immunosuppresseurs sont egalement rapportees, sous forme de syndromes de microangiopathie thrombotique (MAT) ou d’encephalopathie posterieure reversible (PRES). Enfin, des reactions d’hypersensibilite aux anticorps monoclonaux peuvent se manifester par des troubles de la regulation tensionnelle ou d’authentiques etats de chocs secondaires a des reactions de type anaphylactoide a certains produits de chimiotherapie. Ces complications doivent etre evoquees et depistees par le reanimateur lorsqu’un patient immunodeprime est admis en reanimation. Leur prise en charge est majoritairement symptomatique et non specifique, fondee sur les recommandations generales. Leur caractere potentiellement reversible doit encourager une prise en charge maximaliste.

Background Data are scarce about ICU patients with malignancy and severe pulmonary embolism. Here, our main objective was to identify risk factors for life-threatening complications, organ failures, and death in ICU patients with severe pulmonary embolism, with special attention to the impact of malignancy. We also described the clinical features of PE in patients with and without malignancies. Methods Data from consecutive adults admitted to our ICU in 2002-2011 with severe pulmonary embolism were collected retrospectively. Multivariate analysis was performed to look for factors associated with death, organ failures, or life-threatening complications (major bleeding, recurrent PE, and cardiac arrest). Results Of 119 included patients (42 [35%] with bilateral pulmonary embolism), 41 had solid malignancies, 27 hematological malignancies, and 51 no malignancies. The most common symptoms were syncope (40%) and hemoptysis (18%) in patients with solid and hematological malignancies, respectively. Life-threatening complications occurred in 23 (19%) patients; risk factors were obesity (OR, 13.22; 1.93-90.70), disseminated intravascular coagulation/ischemic hepatitis (OR, 27.06; 5.14-142.46), fluid load ≥ 1000 mL/24 h (OR, 6.42; 1.60-25.76), and solid malignancy (OR, 5.45; 1.15-25.89). Inhospital mortality was 27/119 (23%) and respiratory or circulatory failure developed in 36 (30%) patients. Risk factors for these adverse outcomes were older age (OR, 1.04/year; 1.01-1.07), higher oxygen flow rate (OR, 1.28/L; 1.13-1.45); and renal failure (OR, 8.08; 2.50-26.11); whereas chest pain was protective (OR, 0.13; 0.04-0.48). Conclusion In this study, solid malignancy was a risk factor for life-threatening complications but not for death.

La evaluación uni y multivariada de la conformación corporal de machos y hembras de dos híbridos experimentales de tres vías destinados a la producción de pollos camperos, en comparación con Campero INTA como genotipo de referencia, tanto en términos de un conjunto de medidas lineales registradas antes de la faena como de cuatro índices zoométricos, puso en evidencia una base genética al menos parcialmente independiente para forma y tamaño corporal. El estudio de componentes principales de la proporción de pechuga, pata-muslo y grasa abdominal y del rendimiento a la faena mostró la existencia de fuentes de variación para pechuga y pata-muslo independientes de la grasa corporal así como dos fuentes de variación para pechuga, una de ellas independiente y la otra negativamente asociada con la proporción de pata-muslo. Si bien el análisis multivariado permitió caracterizar a las aves de uno y otro sexo en base a particularidades de potencial trascendencia selectiva no evidentes a partir de los respectivos análisis univariados, las diferencias entre grupos genéticos dentro de sexo no fueron productivamente trascendentes. Las aves de crecimiento lento evaluadas en este trabajo presentan un buen desarrollo muscular, a diferencia de los antiguos pollos de campo, mantienen el dimorfismo sexual propio de la especie y exhiben un fenotipo "tipo faisán" que les es característico y que, junto con una pigmentación variable de su plumaje diferente del blanco puro, los identifica y distingue de los híbridos comerciales propios de la avicultura industrial. En lo referente a los cortes de valor carnicero, pechuga y pata-muslo, los dos cruzamientos experimentales de tres vías evaluados pueden considerarse similares entre sí y similares también al grupo de referencia DOI:http://dx.doi.org/10.19137/cienvet2014-1613

Hyperviscosity syndrome is a life-threatening complication. Clinical manifestations include neurological impairment, visual disturbance and bleeding. Measurement of plasma or serum viscosity by a viscometer assesses the diagnosis. Funduscopic examination is a key exam because abnormalities are well-correlated with abnormal plasma viscosity. Etiologies are various but symptomatic hyperviscosity is more common in Waldenström's macroglobulinemia and multiple myeloma. Prompt treatment is needed: treatment of the underlying disease should be considered, but generally not sufficient. Symptomatic measures aim to not exacerbate blood viscosity while urgent plasmapheresis effectively reduces the paraprotein concentration and relieves symptoms.

Previous studies have provided a limited examination of the expression of the orphan melatonin-related receptor in the pituitary and hypothalamus of human and sheep and retinal tissue in the sheep. The present study reports evidence of conservation of expression in regions of the hypothalamus (dorsal medial hypothalamus, lateral hypothalamus, arcuate nucleus), the epithelial layer lining the third ventricle and the paraventricular thalamic nucleus of the mouse, rat and hamster. An extensive and detailed analysis of melatonin-related receptor mRNA expression in the mouse central nervous system and peripheral tissues is presented. Mapping the distribution throughout the entire mouse brain has revealed new sites of expression in a number of brain nuclei, including preoptic areas, parabrachial nuclei and widespread distribution in the olfactory bulb. Reverse transcriptase-polymerase chain reaction was performed with RNA isolated from peripheral tissues revealing expression of the melatonin-related receptor mRNA in the mouse kidney, adrenal gland, intestine, stomach, heart, lung, skin, testis and ovary. These results suggest a conserved function in neuroendocrine regulation and a potential role in coordinating physiological responses in the central nervous system and peripheral tissues.

In about 20% of patients with malignancies with acute respiratory failure (ARF), no etiology can be determined, whatever the diagnostic strategy used. Lung biopsy could then be a precious diagnostic tool leading to therapeutic adaptations and increasing chances for cure. The aim of this study was to assess the diagnostic contribution of lung biopsy in patients for whom a complete diagnosis strategy failed to identify ARF etiology.All hematology patients admitted for ARF to our ICU between 1995 and 2011, and for whom lung biopsy was performed were included in the study. Lung biopsies were surgical, CT guided, or post-mortem. Histological findings were compared to prebiopsy diagnosis and classified into specific or non-specific diagnosis. Therapeutic impact (or Goldman-class in post-mortem biopsies) was also recorded.Among the 1440 hematology patients with ARF managed during the study period, 21 (1%) biopsies were performed, including 10 post-mortem biopsies. Histological diagnoses were specific in 10 biopsies, non specific in 8 biopsies and lung parenchyma was normal in three patients. In 8/11 (72.7%) alive patients, lung biopsy had lead to therapeutic modifications, including treatment implementation in 5 patients and treatment withdrawal in 3 patients. One out of 10 (10%) patients had minor complications. For the 10 dead patients, only one Goldman-type 1 error was found.Diagnostic lung biopsy is rarely needed in hematology patients with ARF. But, it has a 73% therapeutic impact and has overall no major complications. Contribution from post-mortem biopsies seems less relevant.

The effects of S 12370 (2-[4-benzhydryloxypiperidinoethyl]isoxindole), were studied in vitro. In guinea pig isolated tracheal rings, S 12370 induced a similar competitive inhibition of the contractile responses produced by acetylcholine, histamine and serotonin. However, it did not affect the contractions induced by leukotriene D 4 (LTD 4 ), substance P and U 46619, a stable analogue of thromboxane A 2 . S 12370 induced a concentration-dependent inhibition of the cholinergic component of the contraction induced by electrical field stimulation, whereas it did not influence the sustained nonadrenergic noncholinergic (NANC) excitatory response observed in guinea pig isolated bronchi. S 12370 did not influence the relaxations induced by prostaglandin E 2 , isoprenaline and salbutamol, and did not modify the nonadrenergic noncholinergic inhibitory response induced by electrical field stimulation. In isolated left atria, the negative inotropic effect of acetylcholine was competitively inhibited by S 12370. In binding experiments, S 12370 exhibited similar affinity for M 1 , M 2 , M 3 , M 4 muscarinic receptors and also recognized 5-HT 2 serotonin and H 1 histamine receptor subtypes. In ovalbumin-sensitized animals, the contractile response of isolated tracheal rings produced by exposure to the allergen was not influenced by S 12370. Tracheal rings from sensitized animals preexposed in vitro to the allergen developed a hyporesponsiveness to β-adrenoceptor stimulation. S 12370 prevented the inhibitory effect caused by ovalbumin immune sensitization in the relaxation to isoprenaline. In rat polymorphonuclear neutrophil (PMN) cells, S 12370 up to 10 -5 M did not inhibit the arachidonic acid metabolism. These results suggest that in guinea pig tracheal smooth muscle, S 12370 is a competitive inhibitor of muscarinic, serotonin and histamine receptors and can modulate the β-adrenergic dysfunction induced by immune sensitization. S 12370 may present some therapeutic interest in inflammatory airway diseases.

The present study was designed to point out similarities between the effects on pulmonary circulation caused by hypoxia and by a chemoreceptor stimulant (S1867, an almitrine analog). Isolated rat lungs were perfused at a constant flow with homologous blood and ventilated under normoxic, hypoxic or hyperoxic conditions. (1) At 0.25 microgram/ml, S1867 potentiated the hypoxic pressor response, while at 1 microgram/ml, it induced a significant increase in pulmonary artery pressure (PAP) at 21% O2. (2) Since the expression of an oxygen-binding protein (NADPH-oxidase like) has been demonstrated in the rat carotid bodies, we studied the effects of the NADPH-oxidase inhibitor diphenyleneiodonium (DPI) on HPV and on S1867-induced pulmonary vascular responses. Both responses were totally abolished by DPI (40 microM), whereas the vasoconstriction induced by a thromboxane A2 analog (U46619) remained unchanged. (3) Vascular responses to hypoxia and S1867 (1 microgram/ml) were both reversed by a bolus of the sulfhydryl oxidant diamide (3 mg). (4) The S1867-induced response was prevented and reversed by the supply of inhaled oxygen, which was without action on the vasoconstriction induced by U46619. These results suggest that the almitrine analog and hypoxia act at least partly through the same cellular mechanism, involving a DPI-sensitive protein.

A functional approach of the rabbit portal ischemia was performed on five New Zealand rabbits using magnetic-resonance (MR) imaging and an MR-specific contrast agent for the liver. The hepatic vascularization and the functionality of the phagocytosis cells were both studied with a single low dose of a unique contrast agent-superparamagnetic iron oxide particles (SPIOs). After a rapid i.v. injection of SPIOs, functional vessels and normally perfused liver parenchyma appeared with positive signal enhancement, whereas the ischemic area remained dark (cold spot). After the intravascular time period, the well-known negative enhancement induced by these particles on normal parenchyma was observed, with the difference of the ischemic liver, and could be related to the uptake of SPIOs by functional Kupffer cells.

The impact of a contributive result of kidney biopsy on the management of patients in the intensive care unit (ICU) has not been extensively investigated yet.This was a retrospective study conducted between 2000 and 2011 in five French ICUs. The study included 56 patients. They had at least one non-renal organ failure, as defined by a Sequential Organ Failure Assessment (SOFA) score ≥3 on ICU admission, and kidney biopsy was performed during ICU stay. Kidney samples were obtained by percutaneous (N.=55) or transjugular biopsy (N.=1).The mean Simplified Acute Physiology Score II and total SOFA scores on ICU admission were 52±19 years and 10.3±3.6, respectively. ICU mortality was 23%. The median (interquartile range) time between ICU admission and kidney biopsy was 9 days (5-21). Pathologic findings in the 54 analyzable kidney biopsies were acute tubular necrosis (N.=26), glomerulonephritis (N.=14), acute vascular nephritis (N.=11), acute interstitial nephritis (N.=6), and deposit disease (N.=3). Kidney biopsy was contributive to the management of 40 patients. In 23 of these, new treatments were started, in 13 ongoing treatments were stopped, including four life-sustaining therapies, and in 13 it was decided to start chronic renal replacement. Severe bleeding was observed in 7 patients, with fatal outcome in one case.Kidney biopsy may have a significant impact on the management of critically ill patients. Further studies should be done to identify the groups of ICU patients likely to benefit from the procedure with minimum risk.

The synthesis and elastase inhibitory properties of 1,3,4-trisubstituted and 3,4-disubstituted 2-azetidinones are described. Nine of the synthesized derivatives showed elastase inhibitory activities and four of them were specific against human leukocyte elastase (HLE). 2-Deioxy-2-dithianyl-3,4;5,6-di-O-isopropylidene-D-2-glucosyl group attached to the β-lactam nitrogen atom is related to the specificity against HLE.

A third of cerebrovascular accidents are a complication from carotid artery plaque. In addition to the degree of stenosis, plaque composition and morphology are key elements in determining the probability of complication from the atherosclerotic plaque. High resolution MRI can characterize plaque composition and morphology and therefore help identify unstable plaque. The purpose of this review is to summarize recent concepts on unstable plaque and underlying inflammation. The signal characteristics of the different components of plaque on high resolution MRI then be reviewed. Finally, current morphological and functional criteria for unstable plaque will be discussed.

International audience; To develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE(-/-) mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T I spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 mu m spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice.

This paper proposes a modified Windkessel model applied to the coronary circulation and first pass imaging techniques. A compartmental description of the blood flow is used. The compartments taken into account are the arteries, capillaries, lymphatic and venous systems, extravascular /extracellular and cellular domains. In addition the model includes mass transport by blood flow between compartments. The predictions of the model are presented in the simple case of first pass output concentration curves obtained with MR contrast agent in a non-beating blood perfused pig heart. The first results are obtained for low and high input flows in a normal heart. The last one is a simulation of an ischemic heart behavior. The results are in a good agreement with the experimental data from the normal heart and with the characteristic behavior of the microcirculation in the ischemic heart. In conclusion this method which integrates both pressure-flow-volume and mass transport models would be well adapted for the modelisation or perfusion imaging studies.

To assess the effects of Dy-DTPA-BMA (sprodiamide) on ex-vivo MR imaging of reperfused acute myocardial infarction.Eighteen dogs were subjected to 2-hour coronary artery occlusion followed by 24-hour reperfusion. Dysprosium-chelate (Dy-DTPA-BMA) was injected into 16 dogs. Twenty minutes before their sacrifice. Two dogs did not receive the contrast medium and were used as controls. Excised hearts were imaged on T2-weighted spin-echo sequence (T2W SE) and T2*-weighted gradient recalled echo sequence (T2*W GRE), then sectioned and double-perfused for planimetric comparison.Dy-DTPA-BMA induced myocardial signal loss was detected on T2W SE and on T2*W GRE images. The signal loss was observed at the subendocardial location of the myocardial wall inducing an apparent enlargement of the left ventricle cavity and a thinning appearance of the anterior myocardial wall.Myocyte necrosis diminishes the potency of dysprosium to cause MR imaging signal intensity loss in reperfused myocardial infarction. Pre-infarcted myocardium with potentially reversible viability may be responsible for the effect of the contrast medium.

In this work, the use of a new carrier agent for intravascular laser-polarized 3He imaging is reported. Lipid-based helium microbubbles were investigated. Their average diameter of 3 microm, which is smaller than that of the capillaries, makes it possible to conduct in vivo studies. The NMR relaxation parameters T1, T2, and T2* of a microbubble suspension were measured as 90 s, 300 ms, and 4.5 ms, respectively, and in vivo images of encapsulated 3He with signal-to-noise ratios (SNRs) larger than 30 were acquired. Dynamic cardiac images and vascular images of encapsulated 3He were obtained in rats using intravenous injections of microbubble suspensions. Excellent preservation of 3He polarization through the lung capillaries and heart cavities was observed. The first images of 3He microbubble distributions in the lungs were obtained. Additionally, the potential of this technique for lung perfusion assessment was validated through an experimental embolism model with the visualization of perfusion defects.

This study was designed to characterize the endothelin pathway in an immortalized human adenocarcinoma-derived alveolar epithelial cell line (A549) and human umbilical vein endothelial cell line (HUVEC).The release of ET-1 and big-ET-1 was measured in the incubation medium of both cell lines. The expression of mRNAs coding for the endothelin isoforms (hppET-1, -2, -3), the endothelin converting enzymes (hECE-1a, b, c, and d) and the hETA and hETB receptors was investigated using RT-PCR. The expression of ECE-1 mRNA in various human tissues and in A549 cells was investigated by Northern blot analysis and the subcellular localization of ECE-1 in A549 cells was investigated by immunoblotting using a polyclonal antibody.Under control conditions, HUVEC release both ET-1 and big-ET-1 (ratio 5 to 1) while in A549 cells the big-ET-1 levels were below the threshold of detection. The release of these two peptides was minimally affected by various inhibitors of peptidases. However, in both cell lines phosphoramidon produced a concentration-dependent inhibition of ET-1 release and an enhanced accumulation of big-ET-1. Both HUVEC and A549 cells express the mRNAs for ppET-1, ET-A, and ET-B receptor subtypes and ECE-1 (isoforms ECE-1b, c and/or d). In addition, in HUVEC the mRNAs for ppET-2 and for the isoform ECE-1a were also detected. In A549 cells, ECE-1 had a preferential subcellular localization in the membrane fraction but was not detected in the cytosol.Both A549 and HUVEC produce and release endothelin-1 through a specific enzymatic pathway, whether or not ECE-1 is the only enzyme involved remains to be determined. A549 might be used as a screening assay for drug discovery such as for inhibitors of endothelin-1 release.

The neurohormone melatonin is the central switch of the circadian rhythm and presumably exerts its activities through a series of receptors among which MT1 and MT2 have been widely studied. The third binding site of melatonin, MT3, has been recently characterized as a melatonin-sensitive form of the quinone reductase 2 (QR2, EC 1.6.99.2). In the present work, we showed that the binding of melatonin at MT3/QR2 was better described with 2-[125I]-iodomethoxy-carbonylamino-N-acetyltryptamine (2-[125I]-I-MCA-NAT) and, most importantly, that it was measurable at 20 degrees while it has been initially described and thoroughly studied using 2-[125I]-iodomelatonin at 4 degrees. Under these novel conditions, binding to MT3 could be traced without cross-reactivity with MT1 and MT2 receptors and, moreover, under conditions similar to those used to measure MT3/QR2 catalytic activity. The pharmacology established here on hamster kidney samples using the reference compounds remained essentially as already described using other experimental conditions. A new series of compounds with nanomolar affinity for the MT3 binding site and a high MT3 selectivity versus MT1 and MT2 is reported. In addition, we further document the MT3/QR2 binding site by demonstrating that it was widely distributed among mammals, although inter-species and inter-tissues differences exist. The present report details new experimental conditions for the pharmacological study of melatonin-sensitive QR2 isoforms, and suggests that, in addition to an already demonstrated inter-species difference, inter-tissues differences in QR2 sensitivity to melatonin may exist in primates and, therefore, represent an original and interesting route of investigation on the effect of melatonin on MT3/QR2.

Previous studies have provided a limited examination of the expression of the orphan melatonin-related receptor in the pituitary and hypothalamus of human and sheep and retinal tissue in the sheep. The present study reports evidence of conservation of expression in regions of the hypothalamus (dorsal medial hypothalamus, lateral hypothalamus, arcuate nucleus), the epithelial layer lining the third ventricle and the paraventricular thalamic nucleus of the mouse, rat and hamster. An extensive and detailed analysis of melatonin-related receptor mRNA expression in the mouse central nervous system and peripheral tissues is presented. Mapping the distribution throughout the entire mouse brain has revealed new sites of expression in a number of brain nuclei, including preoptic areas, parabrachial nuclei and widespread distribution in the olfactory bulb. Reverse transcriptase-polymerase chain reaction was performed with RNA isolated from peripheral tissues revealing expression of the melatonin-related receptor mRNA in the mouse kidney, adrenal gland, intestine, stomach, heart, lung, skin, testis and ovary. These results suggest a conserved function in neuroendocrine regulation and a potential role in coordinating physiological responses in the central nervous system and peripheral tissues.

The aim of this study was to determine whether the use of a magnetic resonance (MR) susceptibility contrast medium, dysprosium diethylenetriamine pentaacetic acid-bismethylamide (Dy DTPA-BMA; Sprodiamide), may characterize myocardial perfusion abnormalities in a dog model of 90 minutes of coronary occlusion followed by 24 hours of reperfusion (no-reflow phenomenon installed). First-pass MR imaging after an intravenous bolus administration of the contrast agent was performed at the end of reperfusion. Signal intensity analysis on MR imaging, planimetry of pathological data, and blood flow determination were obtained by reference methods for comparison. Dogs were separated into two groups according to the level of collateral blood flow level (group I,22.5 % of the flow in the non-ischemic zone; group II,22.5 % of the flow in the non-ischemic zone). Signal intensity-time curves in the ischemic and non-ischemic left ventricle walls were extracted. Mean collateral blood flow was lower during occlusion in group I (9.8 +/- 5.4%, n = 5) than in group II (38 +/- 12.5%, n = 7, P0.05). Mean infarct size (expressed as a percentage of the area at risk) was significantly larger in group I (low collateral blood flow; 25.3 +/- 14.6%) than in group II (high collateral blood flow; 5.8 +/- 1.1%, P0.05). After rapid injection, a transient decrease of signal intensity induced by Dy DTPA-BMA was observed in both remote and ischemic myocardium but more markedly in remote normally perfused myocardium. Hence, during the transit of a susceptibility-type contrast agent, ischemic myocardium after ischemia and reperfusion appeared as a relative high signal intensity area. First-pass MR imaging with susceptibility contrast agent demonstrated the no- or low-reflow phenomenon. However, the behavior of the myocardial signal intensity-time-related curves did not allow distinction between the two groups of dogs.

The association between body weight-age and egg weight-age patterns was studied in a segregating population of laying hens belonging to the F3 generation of a Rhode Island Red x White Leghorn reciprocal cross. Body weight and egg weight were expressed as a function of time using the model developed by Weatherup and Foster. Each hen was characterized in terms of its asymptotic body weight (ABW), maturing rate for body weight (MBW), asymptotic egg weight (AEW), and maturing rate for egg weight (MEW) values. Four groups of hens were distinguished by means of a principal component analysis. Birds belonging to Groups 1 and 3 were discriminated for their egg weight-age pattern. Group 1 included hens laying the heaviest eggs (AEW = 66.1 g) at the lowest maturing rate (MEW = 0.922), the inverse being true for birds in Group 3 (AEW = 55.7 g and MEW = 0.737). Birds belonging to Groups 2 and 4 were distinguished for their body weight-age pattern. Hens in Group 2 showed the lowest ABW (1,893 g) and MBW (0.764) whereas the heaviest (ABW = 2,802 g) and less mature (MBW = 0.929) birds were found in Group 4. The results confirm the partial pleiotropic basis of the body weight-egg weight correlation, evincing the feasibility of applying selective pressure not only on each character separately but also on maturing rate independently of asymptotic weight within each trait. This strategy could be implemented using a biological selection index based on principal component analysis equations.

Almitrine is a drug used in the treatment of hypoxemic chronic lung diseases such as bronchitis and emphysema because it is a potent stimulant of the carotid bodies in human and different animal species that produces a long-lasting enhancement of alveolar ventilation, ameliorating arterial blood gases. However, the mechanism of action of almitrine remains unknown. We investigated the effect of almitrine on ionic currents of chemoreceptor cells isolated from the carotid body of rat and rabbits by using the whole-cell and inside-out configurations of the patch-clamp technique. Almitrine at concentrations up to 10 microM did not affect whole-cell voltage-dependent K+, Ca2+, or Na+ currents in rat or rabbit cells. However, this concentration of almitrine significantly inhibited the Ca2+-dependent component of K+ currents in rat chemoreceptor cells. This effect of almitrine on the Ca2+-dependent component of K+ currents was investigated further at the single-channel level in excised patches in the inside-out configuration. In this preparation, almitrine inhibited the activity of a high-conductance (152 +/- 13 pS), Ca2+-dependent K+ channel by decreasing its open probability. The IC50 value of the effect was 0. 22 microM. The inhibitory effect of almitrine on Ca2+-dependent K+ channels also was observed in GH3 cells. We conclude that almitrine inhibits selectively the Ca2+-dependent K+ channel and that in rat chemoreceptor cells, this inhibition could represent an important mechanism of action underlying the therapeutic actions of the drug.

1. The effects of tachykinins and capsaicin were studied by means of intracellular membrane potential and isometric tension recordings in the isolated trachea of the guinea-pig. 2. The basal membrane potential averaged -51 mV, and most preparations demonstrated spontaneous slow waves. Tetraethylammonium (TEA), a potassium channel blocker (8 x 10(-3) M), depolarized the membrane potential to -44 mV and induced a rhythmic activity. 3. In control solution, substance P (10(-8)-10(-6) M), [Nle10]-neurokinin A(4-10) (10(-8)-10(-6) M) and capsaicin (10(-7)-10(-6) M) induced concentration-dependent depolarizations which were statistically significant at the highest concentration tested (depolarization by 10(-6) M: 8, 11 and 16 mV for the NK1 agonist, the NK2 agonist and capsaicin, respectively). 4. In the presence of TEA (8 x 10(-3) M), the three substances induced depolarizations which were statistically significant at the highest concentration tested for substance P (10(-6) M) and at 10(-7) and 10(-6) M for both [Nle10]-neurokinin A(4-10) and capsaicin (depolarization by 10(-6) M: 11, 17 and 10 mV for substance P, [Nle10]neurokinin A(4-10) and capsaicin, respectively). 5. In the presence or absence of tetraethylammonium, [MePhe7]-neurokinin B (10(-8)-10(-6) M) did not induce any significant changes in membrane potential. 6. The depolarizing effects of substance P (10(-6) M) and [Nle10]-neurokinin A(4-10) (10(-6) M) were blocked only by the specific antagonists for NK1 and NK2 receptors, SR 140333 (10(-7) M) and SR 48968 (10(-7) M), respectively. The effects of capsaicin (10(-6) M) were partially inhibited by each antagonist and fully blocked by their combination. 7. Substance P (10(-9) to 10(-4) M), [Nle10]-neurokinin A(4-10) (10(-10) to 10(-5) M), [MePhe7]-neurokinin B and capsaicin (10(-7) to 10(-5) M) evoked concentration-dependent contractions. 8. The contractions to substance P were significantly inhibited by SR 140333 (10(-8) to 10(-6) M) but unaffected by SR 48968 (10(-8) to 10(-6) M). Furthermore, the response to [Nle10]-neurokinin A(4-10) was significantly inhibited by SR 48968 and unaffected by SR 140333 at the same concentrations. Although SR 48968 (10(-7) M) alone did not influence the effects of substance P, it potentiated the inhibitory effect of SR 140333 (10(-7) M). A similar synergetic effect of these two compounds was observed in the inhibition of the contractile response to [Nle10]-neurokinin A(4-10). 9. Neither SR 140333 (10(-7) M) nor SR 48968 (10(-7) M) alone influenced the contractions to [MePhe7]-neurokinin B and capsaicin. However, the combination of the two antagonists abolished the contractions to either peptide. 10. These results demonstrate that the stimulation of both NK1 and NK2 tachykinin-receptors induced contraction and depolarization of the guinea-pig tracheal smooth muscle and that both receptors were stimulated during the endogenous release of tachykinins by capsaicin. There was no evidence for a major role of NK3 receptors in the contractile and electrical activity of the guinea-pig isolated trachea.

Therapeutic benefit that can be induced by a pharmaceutical compound partly relies upon the profile of its biological action. Evaluation of the drug-induced effect profile in a given pathological condition begins with the determination of the relevant biological effect related to the therapeutic benefit, which is not always obvious. Evaluation itself is based on dose-effect relationships as a function of time. During chronic treatment, such a kinetic profile oscillates between peak and trough levels. Relationships that can be established between time-dependent effect profile and pharmacokinetic data lead to PK-PD mathematical model, whose main objectives are simulation, prediction of effect and ultimately dose optimisation. The therapeutic implications of the time-dependent effect profile are well illustrated in the cases of antibiotics, diuretics such as furosemide and anti-hypertensive drugs. During drug development, PK-PD approaches can be used in the initial clinical and even pre-clinical phases and can lead to a better definition of effective dose ranges, optimisation of large scale clinical trials or identification of high risk patients. This may favour a reduction of costs and duration of development. Validation of such an approach is easier in well known therapeutic domains but can be more difficult with innovative drugs. The implications of PK-PD approaches can however, be, limited when the relevant biological or clinical parameter cannot be assessed, when the cascade of events leading to pharmacological and therapeutic effects is complex or finally when such PK-PD models require a long time to be established during the early phase of drug development.

An approach is proposed for the design, measurement and data extraction of superconducting microstrip resonators used in determination of surface resistance and penetration depth. Major sources of error are analyzed and procedures to minimize them are given

Resume L’imagerie permet une caracterisation morphologique de la paroi vasculaire et de la plaque d’atherosclerose. L’analyse ex-vivo par immuno-histochimie et biologie moleculaire offre la possibilite d’identifier au niveau de la lesion les acteurs et biomarqueurs de la plaque a risque. L’imagerie moleculaire est une technologie emergente nee des progres spectaculaires de ces deux domaines de recherche, la biologie moleculaire et l’imagerie medicale. Cette nouvelle discipline ouvre des perspectives diagnostiques et therapeutiques notamment dans le domaine du cancer et des pathologies cardiovasculaires. Pour l’atherosclerose, la premiere difficulte est d’identifier la ou les cibles cellulaires et/ou moleculaires les plus pertinentes pour la lesion mais egalement au niveau systemique. En se referant a une liste non exhaustive de biomarqueurs potentiels, les cibles interessantes pour l’imagerie sont : des cellules comme les macrophages qui jouent un role cle dans l’evolution de la plaque, des molecules exprimees au cours du processus inflammatoire, des molecules signatures de la rupture telles que la fibrine. Nous examinerons les differentes strategies d’elaboration de ces nouveaux marqueurs pour l’imagerie de la plaque a risque.

The effects of cAMP-elevating agents on antigen-induced IL-5 (interleukin-5) messenger RNA expression and protein production were examined in vitro in an antigen-driven system of splenocytes from ovalbumin sensitized BALB/c mice. IL-5 production was inhibited by rolipram, a type 4 phosphodiesterase (PDE4) inhibitor, dose-dependently (maximally at 10(-5) M) and by dibutyryl-cAMP (db-cAMP) (3 x 10(-4) M), but not by the type 3 and type 5 PDE inhibitors milrinone and zaprinast (10(-5) M), respectively. Forskolin (10(-5) M), an adenylate cyclase activator, was noninhibitory alone but potentiated inhibition by rolipram. Inhibition was associated with a decrease in IL-5 mRNA expression. Cycloheximide 10(-6) M and actinomycin 2 micrograms/ml abolished IL-5 production and mRNA expression. We conclude that in splenocytes from sensitized mice, IL-5 production and mRNA expression depend on antigen stimulation. The time course of IL-5 protein production is closely related to IL-5 mRNA expression and depends on de novo protein synthesis. db-cAMP and a selective PDE4 inhibitor, alone or in combination with forskolin, are the only cAMP-elevating agents that dose-dependently inhibited antigen-induced IL-5 mRNA expression and protein production. These results are in agreement with in vivo inhibition by a selective PDE4 inhibitor of antigen-induced pulmonary eosinophil infiltration and IL-5 production in sensitized mice, and they suggest that PDE4 inhibitors have potential for treating respiratory allergy.

1. The objective of this study in the hamster cheek pouch was to investigate the role of nitric oxide in bradykinin-induced microvascular leakage. The cheek pouch microcirculatory bed of the anaesthetized hamster was directly observed under microscope and vascular leakage was evidenced by dextranfluorescein isothiocyanate (FITC-dextran) extravasation. 2. Bradykinin superfusion (but not [des-Arg9]-bradykinin up to 3 x 10(-6) M) induced an increase in microvascular permeability (log EC50: -6.5 +/- 0.4) which was exclusively located on the post-capillary venule. Plasma extravasation was blocked by intravenous pretreatment with Hoe 140, a bradykinin B2 receptor antagonist (estimated log ID50: -9.5 +/- 0.2). 3. The effects of bradykinin (3 x 10(-7) M) superfusion were partially but significantly inhibited by indomethacin (10(-5) M, P < 0.05) and abolished by pretreatment with L-nitro-arginine (L-NOARG; 10(-5) M). 4. Acetylcholine (10(-6) M, which releases endothelial nitric oxide (NO), and sodium nitroprusside (10(-6) M, a nitrovasodilator) superfusion did not induce any changes in permeability, per se. Cromakalim (10(-5) M, a potassium channel opener) superfusion induced a moderate but significant plasma extravasation. 5. The effects of bradykinin, blocked by L-NOARG pretreatment, were restored by the co-perfusion of either sodium nitroprusside or cromakalim. Conversely vasoconstriction, produced by a stable analogue of thromboxane A2 (U46619, 3 x 10(-7) M), inhibited the increase in permeability produced by bradykinin. 6. The measurement of arteriolar diameter showed that bradykinin induced a vasodilatation which was blocked by L-NOARG. L-NOARG in itself was a powerful vasoconstrictor. Sodium nitroprusside and cromakalim, in the presence of L-NOARG, were able to restore the inhibited vasodilator response to bradykinin. 7. These results suggest: (1) bradykinin-induced microvascular leakage is mediated by bradykinin B2 receptor activation; (2) the increase in permeability is due to two different independent phenomena, i.e. post-capillary venular endothelial gap formation and arteriolar vasodilatation which increases the post-capillary venular transmural pressure: (3) NO is only involved in the arteriolar dilatation component of the bradykinin-induced increase in microvascular permeability.

A functional approach of the rabbit portal ischemia was performed on five New Zealand rabbits using magnetic-resonance (MR) imaging and an MR-specific contrast agent for the liver. The hepatic vascularization and the functionality of the phagocytosis cells were both studied with a single low dose of a unique contrast agent-superparamagnetic iron oxide particles (SPIOs). After a rapid i.v. injection of SPIOs, functional vessels and normally perfused liver parenchyma appeared with positive signal enhancement, whereas the ischemic area remained dark (cold spot). After the intravascular time period, the well-known negative enhancement induced by these particles on normal parenchyma was observed, with the difference of the ischemic liver, and could be related to the uptake of SPIOs by functional Kupffer cells.

The purpose of this study was to determine the value of three-dimensional time-of-flight MR angiography in screening patients for the presence of renal artery stenoses.Fifty-three patients who were thought to have renovascular hypertension on clinical grounds were prospectively examined with three-dimensional time-of-flight MR angiography. IV digital subtraction angiograms and duplex sonograms were available for all patients. For 21 patients in whom IV angiograms were of high quality and showed the renal arteries to be normal, as confirmed with duplex sonograms, intraarterial digital subtraction angiograms were not obtained for MR correlation. In the other 32 patients, intraarterial angiograms of the abdominal aorta were obtained. MR angiograms were interpreted independently by two radiologists who were unaware of the findings on angiography and duplex sonography. Our preliminary clinical experience suggested that a signal loss in the renal arteries on maximum-intensity-projection MR angiograms indicated a potential stenosis and that the degree of stenosis could not be measured accurately with MR angiography. The search for stenoses was focused on the proximal and middle parts of the vessel, as far as 3 cm from the origin of the vessel. We used intraarterial angiography to measure and grade renal artery stenoses. On intraarterial angiograms, stenoses that involved more than 50% of the vessel's section were considered significant (n = 24) and stenoses that involved 50% or less of the section were considered insignificant (n = 7). These 31 stenoses were found in 26 of the 32 patients who had intraarterial digital subtraction angiography.All 24 significant stenoses appeared as a cutoff of signal intensity on MR angiograms. Results were false-positive in 20 cases: in eight cases, arteries were of small diameter; in seven cases, the stenoses were insignificant; in two cases, the acquisition volume was incorrectly positioned; in two cases, there was a sharp angle in the proximal part of the renal artery; and in one case, no explanation was found. MR angiography had a sensitivity of 100% for detecting stenoses in the proximal 3 cm of the renal artery; stenoses more than 3 cm from the origin of the arteries could not be detected reliably.Our results suggest that three-dimensional time-of-flight MR angiography is a simple method for detecting stenoses of the proximal portion of the main renal arteries. However, more work is needed before widespread clinical use of such a technique is feasible.

This study was designed to determine the effect of the removal of chemical stimuli on breathing rhythmicity in awake newborn lambs; it was also designed to define the chemical threshold below which breathing would stop [arterial PCO2 (PaCO2) apnea threshold]. We used a technique of graded extracorporeal CO2 removal with apneic oxygenation in three groups of animals according to age and carotid body (CB) integrity: < 2 days, CB intact (n = 5); 12 days, CB intact (n = 7); and 12 days, CB denervated (CBD; n = 5). In all animals, whatever their age and CB status, suppression of the chemical drive resulted in sustained apnea. The study, performed at four constant levels of oxygenation (hyperoxia, normoxia, moderate hypoxia, and severe hypoxia), allowed precise determination of the PaCO2 apnea threshold. We found that this PaCO2 apnea threshold depended on the degree of postnatal maturation (it was higher in the younger lambs), the level of arterial oxygenation (it was lowered by hypoxia), and CB status (it was higher in CBD animals). Moreover, we found that the 12-day-old CBD lambs breathe at a level of PaCO2 set close to the point of apnea.(ABSTRACT TRUNCATED AT 250 WORDS)