RESUMEN
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) recipients colonized with vancomycin-resistant Enterococcus (VRE) may have an increased risk of developing VRE bacteremia. Identification of risk factors for the development of subsequent VRE bacteremia among colonized HSCT recipients is necessary to predict which patients may benefit the most from receiving anti-VRE antibiotic therapy as part of an initial antimicrobial regimen when gram-positive bacteremia is suspected. METHODS: This study was a retrospective chart review conducted from May 2008 to May 2011. Adult HSCT patients admitted to the hospital found to have positive VRE surveillance cultures were included. A multivariate analysis was completed to identify risk factors for the development of VRE bacteremia in the study population. RESULTS: Of 152 patients, 19 (13%) patients developed subsequent VRE bacteremia. Risk factors identified for patients with current VRE colonization for VRE bacteremia were the utilization of vancomycin subsequent to VRE surveillance culture positivity (P = 0.017), prolonged duration of neutropenia (P = 0.001), immunosuppression (P < 0.001), and timing of first VRE surveillance screen positivity at week 1 (P = 0.005). A history of VRE colonization on a prior admission was not an independent risk factor for bacteremia in HSCT patients (P = 1.0). HSCT patients with VRE bacteremia had a 30-day all-cause inpatient mortality rate of 29% (P = 0.001). CONCLUSION: HSCT patients receiving immunosuppressive therapy, who have been exposed to vancomycin subsequent to surveillance culture positivity, have had prolonged neutropenia of >30 days, or first surveillance culture positive at week 1 of admission are potential candidates for early implementation of anti-VRE therapy when a gram-positive bacteremia is suspected.
Asunto(s)
Antibacterianos/farmacología , Bacteriemia/epidemiología , Enterococcus/efectos de los fármacos , Infecciones por Bacterias Grampositivas/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Vancomicina/farmacología , Adulto , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Femenino , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Terapia de Inmunosupresión , Control de Infecciones , Masculino , Persona de Mediana Edad , Neutropenia , Estudios Retrospectivos , Factores de Riesgo , Resistencia a la VancomicinaAsunto(s)
Conflicto Psicológico , Cambio Social , Conformidad Social , Población Urbana , Remodelación Urbana , Conflicto de Intereses/economía , Conflicto de Intereses/legislación & jurisprudencia , Francia/etnología , Historia del Siglo XVIII , Historia del Siglo XIX , Cambio Social/historia , Clase Social , Identificación Social , Movilidad Social/economía , Movilidad Social/historia , Población Urbana/historia , Remodelación Urbana/economía , Remodelación Urbana/educación , Remodelación Urbana/historia , Remodelación Urbana/legislación & jurisprudenciaRESUMEN
The development of enteric and sympathetic neurons from neural crest precursor cells is regulated by signals produced by the embryonic environments to which the cells migrate. Bone morphogenetic proteins (BMPs) are present in the developing embryo and act to induce neuronal differentiation and noradrenergic properties of neural crest cells. We have investigated the role of BMP2 in regulating the appearance of distinct populations of autonomic neurons from postmigratory, HNK-1-positive neural crest precursor cells. BMP2 promotes neuronal differentiation of sympathetic and enteric precursor cells isolated from E14.5 rat. The effects of BMP2 change over time, resulting in a decrease in neuron number that can be attributed to apoptotic cell death. BMP2-dependent neuron death is rescued by gut-derived factors that provide trophic support to maturing neurons, indicating that BMP2 regulates the acquisition of trophic dependence of developing peripheral neurons. In addition to regulating neuron number, BMP2 promotes both panneuronal maturation and the acquisition of an enteric phenotype, as measured by lineage-specific changes in the expression of tyrosine hydroxylase and MASH-1. While BMP2 is sufficient to induce neuronal differentiation and panneuronal development, these results suggest that additional factors in the environment must collaborate with BMP2 to promote the final noradrenergic phenotype of sympathetic neurons.
Asunto(s)
Proteínas Morfogenéticas Óseas/farmacología , Sistema Nervioso Entérico/efectos de los fármacos , Cresta Neural/efectos de los fármacos , Neuronas/efectos de los fármacos , Células Madre/efectos de los fármacos , Sistema Nervioso Simpático/efectos de los fármacos , Factor de Crecimiento Transformador beta , Animales , Apoptosis/efectos de los fármacos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Proteína Morfogenética Ósea 2 , Recuento de Células , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Linaje de la Célula/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Proteínas de Unión al ADN/metabolismo , Sistema Nervioso Entérico/citología , Sistema Nervioso Entérico/embriología , Sistema Nervioso Entérico/enzimología , Inmunohistoquímica , Proteínas del Tejido Nervioso/metabolismo , Cresta Neural/citología , Cresta Neural/embriología , Cresta Neural/enzimología , Proteínas de Neurofilamentos/metabolismo , Neuronas/citología , Neuronas/enzimología , Ratas , Ratas Endogámicas , Sistema Nervioso Simpático/citología , Sistema Nervioso Simpático/embriología , Sistema Nervioso Simpático/enzimología , Factores de Transcripción/metabolismoRESUMEN
The development of the enteric nervous system is dependent upon the actions of glial cell line-derived neurotrophic factor (GDNF) on neural crest-derived precursor cells in the embryonic gut. GDNF treatment of cultured enteric precursor cells leads to an increase in the number of neurons that develop and/or survive. Here we demonstrate that, although GDNF promoted an increase in neuron number at all embryonic ages examined, there was a developmental shift from a mitogenic to a trophic response by the developing enteric neurons. The timing of this shift corresponded to developmental changes in gut expression of GFR alpha-1, a co-receptor in the GDNF-Ret signaling complex. GFR alpha-1 was broadly expressed in the gut at early developmental stages, at which times soluble GFR alpha-1 was released into the medium by cultured gut cells. At later times, GFR alpha-1 became restricted to neural crest-derived cells. GFR alpha-1 could participate in GDNF signaling when expressed in cis on the surface of enteric precursor cells, or as a soluble protein. The GDNF-mediated response was greater when cell surface, compared with soluble, GFR alpha-1 was present, with the maximal response seen the presence of both cis and trans forms of GFR alpha-1. In addition to contributing to GDNF signaling, cell-surface GFR alpha-1 modulated the specificity of interactions between GDNF and soluble GFR alphas. These experiments demonstrate that complex, developmentally regulated, signaling interactions contribute to the GDNF-dependent development of enteric neurons.
Asunto(s)
Proteínas de Drosophila , Sistema Nervioso Entérico/embriología , Factores de Crecimiento Nervioso , Proteínas del Tejido Nervioso/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Animales , División Celular/efectos de los fármacos , Sistema Digestivo/embriología , Regulación del Desarrollo de la Expresión Génica , Factor Neurotrófico Derivado de la Línea Celular Glial , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial , Técnicas In Vitro , Ligandos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/farmacología , Cresta Neural/embriología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ret , Ratas , Ratas Sprague-Dawley , Proteínas Tirosina Quinasas Receptoras/genética , Células Madre/efectos de los fármacos , Distribución TisularRESUMEN
Nerve growth factor (NGF) acutely modulates synaptic transmission between sympathetic neurons and their cardiac myocyte targets. NGF also has developmental effects in establishing the level of synaptic transmission between sympathetic neurons and myocytes in culture, although little is known about the mechanisms by which NGF influences this synaptic connectivity. Here we report that NGF acts in conjunction with factors produced by cardiac myocytes to promote neuronal contact with the target and the extension of synaptic vesicle-containing growth cones. In conjunction with previously published results showing that NGF has long-term effects on synaptic transmission between sympathetic neurons and myocytes, this work suggests that NGF acts to promote sympathetic neurotransmission by increasing the number of sympathetic fibers establishing target contact. Further, we found that developmental changes in cardiac myocytes led to an increase in the density of synaptic vesicle-containing variocosities along sympathetic fibers, a process regulated by NGF. Thus, as myocytes mature they produce factors that promote the formation of sympathetic presynaptic structures. These results argue that multiple target interactions regulate the extent of synapse formation between sympathetic neurons and cardiac cells and suggest that NGF promotes presynaptic development by increasing neuronal contact with myocyte-derived cell surface or matrix-associated factors.
Asunto(s)
Miocardio/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Neuronas/metabolismo , Terminales Presinápticos/metabolismo , Sistema Nervioso Simpático/metabolismo , Actinina/metabolismo , Animales , Células Cultivadas , Técnicas de Cocultivo , Medios de Cultivo Condicionados/farmacología , Relación Dosis-Respuesta a Droga , Conos de Crecimiento/efectos de los fármacos , Conos de Crecimiento/metabolismo , Inmunohistoquímica , Uniones Intercelulares/metabolismo , Proteínas de Filamentos Intermediarios/metabolismo , Glicoproteínas de Membrana/biosíntesis , Miocardio/citología , Factor de Crecimiento Nervioso/genética , Factor de Crecimiento Nervioso/farmacología , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Neurofilamentos/genética , Proteínas de Neurofilamentos/metabolismo , Neuronas/citología , Neuronas/efectos de los fármacos , Periferinas , Terminales Presinápticos/efectos de los fármacos , ARN Mensajero/biosíntesis , Ratas , Receptor de Factor de Crecimiento Nervioso/genética , Receptor de Factor de Crecimiento Nervioso/metabolismo , Receptor trkA/genética , Receptor trkA/metabolismo , Sistema Nervioso Simpático/citología , Sistema Nervioso Simpático/efectos de los fármacosRESUMEN
Systematic investigation of acyclic analogs of L-692,429, the prototype benzolactam growth hormone secretagogue, has helped to further define the structural requirements for the release of growth hormone from rat pituitary cells for this class of secretagogues.
Asunto(s)
Benzazepinas/química , Tetrazoles/química , Animales , Benzazepinas/farmacología , Células Cultivadas , Hormona del Crecimiento/metabolismo , Estructura Molecular , Hipófisis/química , Hipófisis/efectos de los fármacos , Ratas , Tetrazoles/farmacologíaRESUMEN
In the peripheral nervous system, enteric and sympathetic neurons develop from multipotent neural crest cells. While local environmental signals in the gut and in the region of the sympathetic ganglia play a role in the choice of cell fate, little is known about the mechanisms that underlie restriction to specific neuronal phenotypes. We investigated the divergence and restriction of the enteric and sympathetic neuronal lineages using immuno-isolated neural crest-derived cells from the gut and sympathetic ganglia. Analysis of neuronal and lineage-specific mRNAs and proteins indicated that neural crest-derived cells from the gut and sympathetic ganglia had initiated neuronal differentiation and phenotypic divergence by E14.5 in the rat. We investigated the developmental potential of these cells using expression of tyrosine hydroxylase as a marker for a sympathetic phenotype. Tyrosine hydroxylase expression was examined in neurons that developed from sympathetic and enteric neuroblasts under the following culture conditions: culture alone; coculture with gut monolayers to promote enteric differentiation; or coculture with dorsal aorta monolayers to promote noradrenergic differentiation. Both enteric and sympathetic neuroblasts displayed developmental plasticity at E14.5. Sympathetic neuroblasts downregulated tyrosine hydroxylase in response to signals from the gut environment and enteric neuroblasts increased expression of tyrosine hydroxylase when grown on dorsal aorta or in the absence of other cell types. Tracking of individual sympathetic cells displaying a neuronal morphology at the time of plating indicated that neuroblasts retained phenotypic plasticity even after initial neuronal differentiation had occurred. By E19.5 both enteric and sympathetic neuroblasts had undergone a significant loss of their developmental potential, with most neuroblasts retaining their lineage-specific phenotype in all environments tested. Together our data indicate that the developmental potential of enteric and sympathetic neuroblasts becomes restricted over time and that this restriction takes place not as a consequence of initial neuronal differentiation but during the period of neuronal maturation. Further, we have characterized a default pathway of adrenergic differentiation in the enteric nervous system and have defined a transient requirement for gut-derived factors in the maintenance of the enteric neuronal phenotype.
Asunto(s)
Cresta Neural/embriología , Nervios Periféricos/embriología , Animales , Apoptosis/genética , Diferenciación Celular , División Celular , Linaje de la Célula/genética , Células Cultivadas , Regulación Enzimológica de la Expresión Génica , Inmunohistoquímica , Neuronas/metabolismo , Fenotipo , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas , Proteínas Tirosina Quinasas Receptoras/genética , Receptor trkA/genética , Receptor trkC , Receptores de Factor de Crecimiento Nervioso/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tirosina 3-Monooxigenasa/genéticaRESUMEN
Plasmacytoma of the jaw bones and oral cavity, as in other anatomic sites, comprises three distinct entities: multiple myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma. This article is a retrospective study of 13 cases; 9 occurred in the mandible and 4 in the maxilla. The most common radiographic finding was a radiolucency that many times was superimposed on the roots or apices of nearby teeth. The most common symptom was localized pain, and the most frequent clinical sign was a raised red lesion on the alveolar ridge. The disease affects older persons, and the posterior mandible is the most frequently reported location. The degree of dysplasia of tumor cells was evaluated as there is a reported correlation with survival rates.
Asunto(s)
Neoplasias Maxilomandibulares/patología , Plasmacitoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias Gingivales/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The 3-substituted benzazepinone, L-692,429 (compound 1), is the prototype compound of a novel class of compounds that stimulate release of growth hormone (GH). The molecule evolved from efforts to identify a non-peptide mimic of the growth hormone-releasing hexapeptide, GHRP-6. Compound 1 is prepared by sequential attachment of dimethyl-beta-alanine and 2'-biphenylyltetrazole side chains to a chiral 3-aminobenzolactam nucleus. Comparison of the biological activity of 1 with the corresponding six- and eight-membered lactam analogs shows the seven-membered benzazepinone skeleton to be preferred. Molecular modeling of the structurally diverse GH secretagogues, L-692,429 and GHRP-6, was performed.
Asunto(s)
Benzazepinas/farmacología , Tetrazoles/farmacología , Secuencia de Aminoácidos , Animales , Benzazepinas/química , Células Cultivadas , Hormona del Crecimiento/análogos & derivados , Masculino , Datos de Secuencia Molecular , Estructura Molecular , Oligopéptidos/farmacología , Ratas , Ratas Wistar , Relación Estructura-Actividad , Tetrazoles/químicaRESUMEN
Cholecystectomy causes alterations in bile composition. In particular it rises the proportion of highly detergent bile acids with the possible consequence of the manifestation of dyspepsia in a high percentage of patients: this is the well-known post-cholecystectomy syndrome. In this clinical trial we studied the activity and safety of tauroursodeoxycholic acid--TUDCA--(500 mg/die) in the prevention of dyspepsia in cholecystectomized patients, in comparison with no treated group. We enrolled 203 patients (101 TUDCA--group A--and 102 control-group B). The two groups were comparable for age (47.1 years in group A and 50.7 years in group B), sex (m/f: 28/73 and 37/65 in the two groups) and for other characteristics connected to surgical procedures. After operation all patients suffered from dyspepsia symptoms. In patients treated with TUDCA we registered a prompt regression in severity of symptoms when compared with no treated group: in fact we noted a significant difference only at the first control planned after one month from operation. No difference were registered at the other controls (two and three months after operation). Two patients in A and 3 in group B manifested adverse events. In conclusion, the treatment with TUDCA, a new hydrophilic bile acid, seems to contribute to the improvement of clinical course in cholecystectomized patients.
Asunto(s)
Colecistectomía , Dispepsia/prevención & control , Complicaciones Posoperatorias/prevención & control , Ácido Tauroquenodesoxicólico/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Colecistectomía/efectos adversos , Dispepsia/etiología , Femenino , Estudios de Seguimiento , Humanos , Isomerismo , Masculino , Persona de Mediana EdadRESUMEN
Identifying the point of apical termination in endodontic therapy is of indisputable importance. In this study, the accuracy of an electronic apex locator was clinically evaluated in 26 maxillary molar teeth, and comparisons were made to the radiographic and direct anatomical measurements of tooth length. The results indicated that a higher percentage of acceptable measurements were obtained by the radiographic method as compared with the electronic method (88.5% to 73.1%). Additionally, inaccurate electronic estimates were long in every instance. The results of this study do not support the replacement of radiographs with electronic devices in endodontic therapy.
Asunto(s)
Preparación de la Cavidad Dental/instrumentación , Cavidad Pulpar/anatomía & histología , Tratamiento del Conducto Radicular/instrumentación , Anciano , Humanos , Masculino , Maxilar , Persona de Mediana Edad , Diente Molar/anatomía & histología , Odontometría/instrumentación , Raíz del Diente/anatomía & histologíaAsunto(s)
Venenos de Abeja/análisis , Oligopéptidos/aislamiento & purificación , Piel/análisis , Venenos de Avispas/análisis , Secuencia de Aminoácidos , Animales , Anuros , Quimiotaxis de Leucocito/efectos de los fármacos , Liberación de Histamina/efectos de los fármacos , Datos de Secuencia Molecular , Oligopéptidos/farmacología , Ranidae , Homología de Secuencia de Ácido Nucleico , Especificidad de la EspecieRESUMEN
The hydroxylation of tyrosine to dopa is the rate-limiting reaction in catecholamine biosynthesis. It has been previously reported that secretin, vasoactive intestinal peptide and peptide histidine isoleucine amide, all members of the secretin-glucagon family of peptides, increase dopa synthesis in superior cervical ganglia in vitro. We report here that two other members of this peptide family, rat growth hormone-releasing factor and helodermin H38, a component of Gila monster venom, also increase the rate of dopa synthesis, while glucagon-like peptides I and II and a number of other peptides tested produce no effect. Since analogs of cAMP also increase dopa synthesis, it is of particular interest that all of the peptides that increase catechol synthesis also raise the levels of this cyclic nucleotide in the superior cervical ganglion. Helodermin H38 stimulated the rate of dopa synthesis and the level of cAMP with similar potencies (EC50S of approximately 10 nM) and with maximal effects of two- and two-fold, respectively. By either measure, rat growth hormone-releasing factor produced a two-fold increase at 10 microM and a three- to four-fold increase at 30 microM. Analogs of peptides of the secretin-glucagon family with a deletion or modification of the N-terminal histidine were much less effective in these assays at the concentrations tested than were their parent compounds, demonstrating an important role for this amino acid in conferring activity on these peptides. In addition to increasing dopa synthesis in intact tissue, incubation of ganglia with rat growth hormone-releasing factor, secretin, vasoactive intestinal peptide or peptide histidine isoleucine amide also increased the activity of tyrosine hydroxylase measured subsequently in ganglion homogenates. Thus, the peptidergic stimulation of dopa synthesis observed in the intact superior cervical ganglion appears to be due, at least in part, to the activation of tyrosine hydroxylase. Together with previous studies, these findings support the hypothesis that certain members of the secretin-glucagon family increase catecholamine synthesis in sympathetic neurons by a cAMP-dependent activation of tyrosine hydroxylase.
Asunto(s)
Ganglios Simpáticos/enzimología , Hormona Liberadora de Hormona del Crecimiento/farmacología , Péptidos/farmacología , Tirosina 3-Monooxigenasa/metabolismo , Secuencia de Aminoácidos , Animales , Ganglios Simpáticos/efectos de los fármacos , Péptidos Similares al Glucagón , Técnicas In Vitro , Péptidos y Proteínas de Señalización Intercelular , Masculino , Ratas , Ratas EndogámicasRESUMEN
In order to establish whether CyP is the pharmacologically relevant CsA receptor, the CyP binding v immunosuppressive activity was measured for an extensive, structurally varied group of CsA analogues. Overall, CyP binding was found to parallel immunosuppressive activity. Other than MeAla6-CsA, the few exceptions to the correlation could be ascribed to cellular metabolism. These results strongly implicate CyP or a related protein in the mechanism of action of cyclosporine.
Asunto(s)
Proteínas Portadoras/metabolismo , Ciclosporinas/metabolismo , Terapia de Inmunosupresión , Inmunosupresores , Activación de Linfocitos/efectos de los fármacos , Animales , Éteres/farmacología , Técnicas In Vitro , Interleucina-2/metabolismo , Ionomicina , Prueba de Cultivo Mixto de Linfocitos , Ratones , Isomerasa de Peptidilprolil , Relación Estructura-Actividad , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
The subject of background variables influential in the choice of postgraduate medical specialty training has been described in numerous papers. Few, if any, have examined the influential patterns in minority students' residency training selection when compared with nonminority students. No studies reviewed examined the differential patterns that may have an impact on specialty selection in these subgroups, especially in regard to maternal and paternal educational status. This study analyzes the interrelationship between minority and nonminority medical students, their parental educational background, and selection of postgraduate specialty, and suggests that parental educational background be investigated further as a predicative indicator of medical student specialty career selection.
Asunto(s)
Selección de Profesión , Internado y Residencia , Grupos Minoritarios , Padres , Estudiantes de Medicina/psicología , Escolaridad , Humanos , Louisiana , Medicina , Especialización , Estados UnidosRESUMEN
Lysosomotropic detergents, which kill mammalian cells by disrupting lysosomal membranes, have now been found to be antifungals also. All strains in our assay are susceptible. The mode of action is as yet undetermined, but intracellular vacuoles may be the primary targets.
Asunto(s)
Detergentes/farmacología , Hongos/efectos de los fármacos , Lisosomas/efectos de los fármacos , Tensoactivos/farmacología , Candida/efectos de los fármacos , Hongos/ultraestructura , Concentración de Iones de Hidrógeno , Imidazoles/farmacología , Cetoconazol/farmacología , Saccharomyces cerevisiae/efectos de los fármacos , Vacuolas/efectos de los fármacosRESUMEN
The continuing discovery and development of beta-lactams as antibiotics has had an unparalleled impact on the overall health and well-being of society. Recently, appropriately substituted cephalosporins were shown to be potent inhibitors of elastase, suggesting a novel therapeutic role for the beta-lactams in the control of emphysema and other degenerative diseases. We have now solved and partially refined at atomic resolution the structure of a complex of porcine pancreatic elastase with the time-dependent irreversible inhibitor 3-acetoxymethyl-7-alpha-chloro-3-cephem-4-carboxylate-1,1-dioxide tert-butyl ester (I), the most potent of the beta-lactam elastase inhibitors yet reported. (Porcine pancreatic elastase is a close relative of the desired drug target, human polymorphonuclear leukocyte elastase.) A mechanism of action is presented, based on the structure and on biochemical evidence (T.-Y.L. et al., in preparation), which clarifies the operational similarities and differences between beta-lactam elastase inhibitors and antibiotics. Features of the reaction include the expulsion of a leaving group at the cephalosporin 3' position and the formation of two covalent bonds with the active site of porcine pancreatic elastase at residues Ser 195 and His 57.
Asunto(s)
Antibacterianos/metabolismo , Lactamas , Elastasa Pancreática/metabolismo , beta-Lactamas , Animales , Antibacterianos/farmacología , Sitios de Unión , Modelos Moleculares , Elastasa Pancreática/antagonistas & inhibidores , Unión Proteica , Conformación Proteica , Porcinos , Difracción de Rayos XRESUMEN
Our previous studies in cortical collecting ducts isolated from rat kidneys have shown that vasopressin increases both sodium absorption and potassium secretion, while bradykinin inhibits sodium absorption without affecting potassium transport. To determine which anions are affected by these agents, we perfused cortical collecting ducts from rats treated with deoxycorticosterone and measured net chloride flux, net bicarbonate flux (measured as total CO2), transepithelial voltage, and the rate of fluid absorption. Arginine vasopressin (10(-10) M in the peritubular bath) caused a sustained sixfold increase in net chloride absorption and a two- to threefold increase in the magnitude of the lumen negative transepithelial voltage. Before addition of vasopressin, the tubules secreted bicarbonate. Vasopressin abolished the bicarbonate secretion, resulting in net bicarbonate absorption (presumably due to proton secretion) in many tubules. Bradykinin (10(-9) M added to the peritubular bath) caused a reversible 40% inhibition of net chloride absorption, but did not affect the transepithelial voltage or the bicarbonate flux. We concluded: (a) that arginine vasopressin stimulates absorption of chloride and inhibits bicarbonate secretion (or stimulates proton secretion) in the rat cortical collecting duct; and (b) that bradykinin inhibits net chloride absorption in the rat cortical collecting duct without affecting transepithelial voltage or bicarbonate flux. Combining these results with the previous observations on cation fluxes described above, we conclude that bradykinin inhibits electroneutral NaCl absorption (or stimulates electroneutral NaCl secretion) in the rat cortical collecting duct.